Photodynamic therapy has been applied endoscopically to treat early esophageal cancer. However, the long-term survival outcome of this treatment option is unknown in literature. Patients and Method: The patients of early esophageal cancer (clinical stage I) treated with photophrin based photodynamic therapy were analyzed for their long-term survival outcome and compared to those patients undergoing esophagectomy by a single surgeon for stage I disease. Results: There were 15 and 16 patients undergoing PDT and esophagectomy enrolled in the current study respectively. Complete response was achieved in 10 (66.7%) patients after PDT. After adjuvant chemoradiation (CCRT) complete response was achieved in 13 patients (86%). There is no mortality after PDT. Severe complication was detected in 3 patients including trachea-esophageal fistulae, esophageal stenosis and skin photosensitivity respectively. With a median follow-up duration of 110.2 months (+9.6 months) for the patients after PDT, there were 4 and 3 recurrence in the primary tumor site and regional lymph node respectively with 73.3% of successful local control rate of the primary tumor. There were 7 (46.7%) patients died during clinical follow-up of this cohort with 5 (33.3%) from disease progression of esophageal cancer and two from other diseases respectively. The five-year survival rate after PDT is 64.3%, whereas 70.9% of the patients after esophagectomy without significant difference of these two group of patients (P=0.72). Conclusion: Our preliminary results suggested that PDT might provide an equivalent long-term oncological outcome as compared to that done by esophagectomy for early esophageal cancer. A prospective randomized clinical trial comparing the results with esophagectomy and other endoscopic abrasive therapies is warrant in the future.

In this review, we have included current information on the use of photodynamic therapy in the treatment of gliomas. We mainly focused on the discussion and regarding the use of photodynamic therapy in patients with genetically determined syndromes that are associated with an increased risk of glioma. The review also uses information on genetic syndromes that are associated with an increased risk of glioma.

Photodynamic therapy (PDT) of cancer is dependent on three primary components: photosensitizer (PS), light, and oxygen. Because these components are interdependent and vary during the dynamic process of PDT, assessing PDT efficacy may not be trivial. Therefore, it has become necessary to develop pre-treatment planning, on-line monitoring and dosimetry strategies during PDT, which become more critical for two or more chromophore systems, e.g. PS-CD conjugates developed in our laboratory for fluorescence-imaging and PDT of cancer. In this study, we observed a significant impact of variable light dosimetry; (i) high light fluence and fluence rate (light dose: 135 J/cm², fluence rate: 75 mW/cm²) and (ii) low light fluence and fluence rate (128 J/cm² and 14 mW/cm² and 128 J/cm² and 7 mW/cm²) in photobleaching of the individual chromophores and their long-term tumor response. The fluorescence at the near-infrared (NIR) region of the PS-NIR fluorophore conjugate was assessed intermittently via fluorescence imaging. The loss of fluorescence, photobleaching, caused by singlet oxygen from the PS was mapped continuously during PDT. The tumor responses (BALB/c mice bearing Colon26 tumors) were assessed after PDT by measuring tumor sizes daily. Our results showed distinctive photobleaching kinetics rates between the PS and CD. Interestingly, compared to higher light fluence, the tumors exposed at low light fluence showed reduced photobleaching and enhanced long-term PDT efficacy. The presence of NIR fluorophore in PS-CD conjugates provides an opportunity of fluorescence imaging and monitoring the photobleaching rate of the CD moiety for large and deeply seated tumors and assessing PDT tumor response in real-time.

This paper presents the rationale for using ultra low intensity transcranial light photodynamic treatment (LIT-PDT) for treating glioblastoma. Glioblastoma is currently treated with maximal safe resection, temozolomide and ionizing irradiation. Mortality in 2024 remains at over 80% within several years from diagnosis. 5-aminolevulinic acid (5-ALA) is a heme precursor that is selectively taken up preferentially by malignant cells, including glioblastoma. Photon energy can be transduced to molecular oxygen by a 5-ALA metabolite, PpIX, transforming oxygen to the singlet state, a reactive oxygen species (ROS) that destroys or damages vital glioblastoma cell structures. In PDT, light energy ~ 100 to 200 J / cm2, at 630 nm is delivered intraoperatively after resection and preoperative oral 5-ALA. This generates ROS cytotoxicity in residual glioblastoma cells within the resection cavity wall. 630 nm light poorly penetrates skin, skull, and brain tissue. That currently restricts PDT to a single intraoperative session using high flux light. LIT-PDT addresses some current shortcomings of 5-ALA PDT treatment. Part 1 analyzes published data indicating that continuous ultra low light flux, 17 μW / cm2, over 24 hours for a total delivery of 1.5 J / cm2, is effective for 5-ALA PDT treatment. That opens the way for repetitive, extracranial light to deliver enough energy for low flux, long duration PDT to any deep brain structure using less than 12 W total distributed over the entire scalp area. In Part 2, by analysis of 5-ALA and PpIX physiology, it became apparent that four non oncology drugs - ciprofloxacin, deferiprone, telmisartan and ziprasidone, will increase energy capture by GB cells, thereby increasing PDT treatment cytotoxicity. A phased pilot study of LIT-PDT treatment is being planned.

Over the last 20 years, gliomas have made up over 89% of malignant CNS tumor cases in the American population (NIH SEER). Within this, glioblastoma is the most common subtype, comprising 57% of all glioma cases. Highly aggressive, this deadly disease is known for its high genetic and phenotypic heterogeneity, rendering a complicated disease course. The current standard-of-care consists of maximally safe tumor resection concurrent with chemoradiotherapy. However, despite advances in technology and therapeutic modalities, rates of disease recurrence are still high and survivability remains low. Given the delicate nature of the tumor location, remaining margins following resection often initiate disease recurrence. Photodynamic therapy (PDT) is a therapeutic modality that, following the administration of a non-toxic photosensitizer, induces tumor-specific anti-cancer effects after localized, wavelength-specific illumination. Its effect against malignant glioma has been studied extensively over the last 30 years, in pre-clinical and clinical trials. Here, we provide a comprehensive review of the three generations of photosensitizers alongside their mechanisms of action, limitations, and future directions.

The Ce0.5Y0.35Tb0.15F3 nanoparticles with CeF3 hexagonal structure were synthesized by co-precipitation technique. The average nanoparticle diameter was 14±1 nm. The luminescence decay curves of Ce0.5Y0.35Tb0.15F3 nanoparticles (λem = 541 nm, 5D4 – 7F5 transition of Tb3+) conjugated with Radachlorin by means of polyvinylpyrrolidone coating as well as without Radachlorin were detected. Efficient nonradiative energy transfer from Tb3+ to the Radachlorin was demonstrated. The maximum energy transfer coefficient for nanoparticles conjugated with Radachlorin via polyvinylpyrrolidone and without the coating were 82% and 55%, respectively. The average distance between nanoparticle surface and Radachlorin was R0 =4.5 nm. The best results for X-ray induced cytotoxicity was observed for NP-PVP-Rch sample at the lowest Rch concentration. In particular, after X-ray irradiation the survival A 549 human lung carcinoma cells decreased by ~12%.

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes, despite the prevalent recurrence and progression among many patients. In particular, flat urothelial car-cinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new‐generation photosensitizer, 5‐Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence, and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

Staphylococcus aureus is a gram-negative bacterium that causes superficial and deep infections that can be mild or potentially fatal. Recently, the bacterium has gained significant attention due to the increased incidence of multidrug-resistant (MDR) strains that make treatment with antibiotics dif-ficult. Owing to the MDR strains, alternative therapies such as antimicrobial photodynamic therapy (PDT) have emerged as good options to treat non-systemic infections. PDT combines a photosensi-tiser (PS) with light and oxygen to generate free radicals that destroy bacterial structures such as the plasma membrane, matrix, and genetic material. This systematic review aimed to identify the ef-fectiveness of PDT delivered using different types of hydrogels for treating wounds, burns, and contamination by S. aureus. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Bibliographic research was conducted using the PubMed, Web of Science, and Scopus databases. Only full articles published in English between 2013 and 2024 from any country of origin (without restrictions) were included. The research was carried out from 15 June 2023 to 15 June 2024 and did not use any automatic biblio-graphic search tool. The articles collected were identified using keywords and selected using in-clusion and exclusion criteria in accordance with the PRISMA protocol. Seven articles were in-cluded that presented a good set of evidence associated with the use of PDT against S. aureus in in vitro and in vivo studies. To conclude, PDT can effectively complement antimicrobial therapy against S. aureus, in the healing of wounds and burns. The effectiveness of this technique depends on the PS used, hydrogel type, and lesion location. Some studies have already demonstrated the ef-fectiveness of PDT but most were in vitro and a few in vivo. Further studies are required to demonstrate the safety and efficacy of PDT delivered via hydrogels in in vivo models of bacterial infection.

Cancers, a large and heterogeneous group of malignancies, are becoming an increasingly important cause of premature mortality worldwide. 2% of these are primary CNS tumors, of which 24% are gliomas. These tumors are diverse, but what they have in common is one of the most unfavorable prognoses among all cancers. A patient's future varies depending on the grade of the diagnosed glioma. To date, however, no standard treatment for grade IV has been established. All glioblastomas eventually undergo progression or recurrence. The current standard of treatment, which includes surgical intervention, radiation therapy and chemotherapy, is therefore far from sufficient. Work is constantly underway to discover a new, effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound - a photosensitizer (PS), which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating activation processes leading to the formation of reactive oxygen species and selective destruction of inappropriate cells. Currently, this method has been approved for the treatment of several cancers. Research focusing on the effective use of PDT in glioma therapy is already underway, with promising results. In our work, we present molecular insights into PDT of glioma. Based on the available literature, we analyze and systematize the impact of various molecules, proteins, transporters and transmitters on the efficacy of PDT and the effect of PDT on their expression. In addition, we highlight gaps in current knowledge and point out directions for future research that may contribute to the efficacy of PDT glioma.

Microbiological control of dental pathologies presents a significant clinical challenge for dental surgeons, particularly considering drug-resistant microorganisms. To address this issue, Antimi-crobial Photodynamic Therapy (PDT) has emerged as an effective and complementary technique for microbial reduction. This therapy involves the application of a photosensitizer dye (PS) either topically or systemically, followed by exposure to low-power lasers with appropriate visible light wavelengths. PDT has found a valuable place in dentistry across various specialties, including surgery, periodontics, endodontics, dentistry, implantology, orthodontics, and pediatrics. In the realm of pediatric dentistry, managing microorganisms during dental treatments has become a major challenge.This article reviews the evidence supporting the potential of photodynamic therapy in combating bacteria, fungi, and viruses, with a particular focus on areas such as endodontics, restoration in deciduous teeth, implantology, and periodontics for bacterial control. Additionally, PDT has shown promise in stomatology, specifically in the treatment of mucositis and herpes. Considering its promising results and ease of application, photodynamic therapy presents an in-teresting alternative for clinical practice. However, it is important to note that specific protocols must be followed for each application, encompassing the type of photosensitizer, concentration, pre-irradiation time, light type, wavelength, energy, power, and mode of light delivery. Researchers have been steadily refining these protocols to facilitate PDT's integration into clinical practice.

Background: To compare photodynamic therapy 41 and the use of probiotics in reducing halitosis assessed through gas chromatography and microbiome analysis. Methods: Participants aged from 18 to 25 years, showing sulfide (SH2) ≥ 112 ppb on gas chromatography, were selected. They were divided into 4 treatment groups: Group 1 - Tongue Scraping; Group 2- Antimicrobial Photodynamic Therapy (aPDT); Group 3- Probiotics; Group 4- Antimicrobial Photodynamic Therapy (aPDT) and Probiotics. The halimetry process was performed before, immediately after the treatments, 7 days, 14 days and 30 days after the initial collection. The collections for later microbiological analysis were made along with the halimetry, for the microbiome analysis. Results: Treatment with aPDT or probiotics under these experimental conditions was not able to change the bacteria present in the biofilm of the tongue. Conclusions: More research is needed to know the behavior of the oral microbiome in the presence of halitosis and the effectiveness of new treatments.

A single-site, randomized clinical trial was designed to determine the efficacy of regular home use of Lumoral® dual-light antibacterial aPDT in periodontitis patients. For the study, 200 patients are randomized to receive non-surgical periodontal treatment (NSPT), including standardized hygiene instructions and electric toothbrush, and scaling and root planing, or NSPT with adjunctive Lumoral® treatment. A complete clinical intraoral examination is conducted in the beginning, at three months, and at six months. This report presents the three-month results of the first 59 consecutive randomized subjects. At three months, bleeding on probing (BoP) was lower in the NSPT+Lumoral®-group than in the NSPT group (p=0.045), and more patients in the NSPT+Lumoral®-group had their BoP below 10% (52% vs. 29%, respectively, p=0.008). Patients in the NSPT+Lumoral®-group improved their oral hygiene by visible-plaque-index (p=0.0002), while the NSPT group showed no statistical improvement as compared to baseline. Both groups significantly reduced the number of deep periodontal pockets, but more patients with a reduction in their deep pocket number were found in the NSPT+Lumoral® group (92% vs. 63%, p=0.01). Patients whose number of deep pockets was reduced by 50% or more were also more frequent in the NSPT+Lumoral®-group (70% vs. 33%, p=0.01). Patients with initially less than ten deep pockets had fewer deep pockets at three-month follow-up in the Lumoral® group (p=0.02). In conclusion, adjunctive use of Lumoral® in NSPT results in improved treatment outcomes at three months post-therapy.

Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and N-methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and FACS analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and H&E and TUNEL staining analyses were performed and compared between small (tumor volume of <50 mm³) and large (tumor volume of >50 mm³) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.

Photodynamic therapy has emerged as a non-invasive treatment modality for various diseases, leveraging photosensitizing compounds to induce localized cytotoxicity upon light activation. This review explores the isolation and characterization of photosensitizing compounds sourced from microalgae, focusing on their potential applications in photodynamic therapy. Microalgae represent a rich source of bioactive molecules, including chlorophylls, phycobiliproteins, and carotenoids, which exhibit inherent photosensitizing properties. Methodologies for the extraction and purification of these compounds from different microalgal species are discussed, emphasizing the importance of optimizing extraction techniques to enhance yield and purity. Characterization techniques such as UV-Vis absorption spectroscopy, fluorescence spectroscopy, and mass spectrometry are highlighted for elucidating the chemical structures and photophysical properties of isolated compounds. Furthermore, the review examines the photodynamic efficacy of microalgae-derived photosensitizers through in vitro and in vivo studies, assessing their cytotoxic effects on cancer cells and antimicrobial activity against pathogens. The integration of microalgae-derived photosensitizers into PDT protocols represents a promising avenue for developing sustainable and effective therapeutic strategies, underscoring the potential of these natural compounds in advancing biomedical applications.

Background Endometrial cancer is the fourth most common type of cancer in the world. Due to the prevalence and high morbidity, it is of key importance to make a quick and accurate diagnosis and effective therapy. The use of photodynamic therapy (PDT) in the treatment of endometrial cancer is a significant challenge in conducting clinical trials. PDT is non-invasive, with few side effects, damaging only neoplastic tissue, leaving healthy adjacent structures intact. Thanks to numerous experiments (also in vitro), PDT is gaining more and more recognition as a potential tool in endometrium cancer treatment. Objective The aim of the study was to analyze the effectiveness of photodynamic therapy on endometrial cancer tissue samples Methods In the in vitro experiment of PDT, sections of endometrial cancer tissue taken from female patients were subjected to. Rose Bengal was used as a photosensitizer in order to assess the usefulness of the applied PDT and to introduce these solutions into the in vivo test procedure. Results Changes on the cellular substrate, such as: chromatin condensation, disturbed structure and shape of cell nuclei were observed in all tissues subjected to PDT. Conclusions The PDT experiment in vitro offers opportunities and hopes for using the chosen procedure also in vivo. Keywords endometrial cancer; photodynamic therapy; in vitro; treatment; rose bengal

Background: The extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae is one of the leading causes of health-associated infections (HAI), whose antibiotic treatments have been severely reduced. Besides, HAI bacteria may harbor pathogenic factors such as siderophores, enzymes, or capsules, which increase the virulence of these strains. Thus, new therapies such as antimicrobial photodynamic inactivation (aPDI) are needed. Method: A collection of 118 clinical isolates of K. pneumoniae were characterized susceptibility and virulence through the determination of the minimum inhibitory concentration (MIC) of Amk, Cfx, Cfz, Imp, Mer, and Pip-taz, and by PCR, the frequency of the virulence genes, K2, magA, rmpA, entB, ybtS, and allS. Susceptibility to innate immunity, such as human serum, macrophages, and polymorphonuclear cells, was tested. All the strains were tested for sensitivity to the photosensitizer PSIR-3 (4µg/mL) in a 17µW/cm2 for 30 min aPDI. Results: A significantly higher frequency of virulence genes in ESBL than non-ESBL bacteria were observed. The isolates of the genotype K2+, ybtS+, and allS+ display enhanced virulence since they showed higher resistance to human serum as well as to phagocytosis. All strains are susceptible to the aPDI with PSIR-3 decreasing viability in 3log10. The combined treatment with Cfx improved the aPDI to 6log10 for the ESBL strains. The combined treatment is synergistic as it showed an FIC index value of 0.15. Conclusions: The aPDT effectively inhibits clinical isolates of K. pneumoniae, including the more risky strains of ESBL-producing bacteria and the K2+, ybtS+, and allS+ genotype. The aPDI with PSIR-3 is synergistic with Cfx.

Direct detection of singlet-state oxygen (1O2) constitutes the holy grail dosimetric method for type-II photodynamic therapy (PDT), a goal that can be quantified using multispectral singlet oxygen near-infrared luminescence dosimetry (MSOLD). The optical properties of tissues, specifically their scattering and absorption coefficients, play a crucial role in determining how the treatment and luminescence light are attenuated. Variations in these properties can significantly impact the spatial distribution of the treatment light and hence the generation of singlet oxygen, and the detection of singlet oxygen luminescence signals. In this study, we investigated the impact of varying optical properties on the detection of 1O2 luminescence signals during Photofrin-mediated PDT in tissue-mimicking phantoms. For comparison, we also conducted Monte Carlo (MC) simulations under the same conditions. The experimental and simulations are substantially equivalent. This study advances understanding of MSOLD dosimetry during PDT.

In recent years, the chemo-photodynamic combinational therapy has become increasingly popular in treating breast cancer. However, the limited accumulation of nanodrugs into tumor (less than 1% of injected dose) extremely impacts therapeutic efficacy. Herein, the photosensitizer Chlorin e6 (Ce6) and the chemotherapeutic drug rhein (Rhe) were self-assembled to form a carrier-free nanodrug (RC NPs) with good stability and high drug loading rate. Ultrasound (US) irradiation was applied to increase the permeability of tumor blood vessels thus greatly enhance the drug accumulation of RC NPs in tumor tissues. After uptake by tumor cells, Ce6 could produce a sig-nificant amount of reactive oxygen species (ROS) when exposed to laser irradiation, while rhein could inhibit tumor cell proliferation and affect mitochondrial membrane potential, inducing tumor cell apoptosis through the mitochondria-dependent apoptosis pathway, thus effectively realizing the combined effect of PDT and chemotherapy. Taken together, RC NPs have an enhanced EPR effect when exposed to US irradiation and exhibit better tumor suppression, which provides new insights into chemo-photodynamic combination treatment for clinical breast cancer.

Antimicrobial photodynamic therapy (aPDT) used to sterilize carious dentin may irritate the pulp tissues because of tissue-penetrating laser and singlet oxygen generation. This study aimed to assess the effects of aPDT on rat pulp tissues. A cavity formed in a rat maxillary first molar was treated with aPDT. The combined photosensitizer and laser irradiation conditions in the aPDT groups were as follows: methylene blue and 100 mW for 60 s, brilliant blue (BB) and 100 mW for 60 s, BB and 50 mW for 120 s, and BB and 200 mW for 30 s. Each cavity was treated with an all-in-one adhesive and filled with flowable resin. aPDT was not applied for the control. In each group, the rats were sacrificed on postoperative days 1 and 14, and thin sections of the treated teeth were prepared. Pulp tissue disorganization (PTD), inflammatory cell infiltration (ICI), and tertiary dentin formation (TDF) were evaluated. At 1 day evaluation, there were significant differences between the aPDT group and controls with respect to PTD and ICI. 14 days later, almost all specimens showed tertiary dentin formation. aPDT caused temporarily reversible injury to the rat dental pulp, which healed with tertiary dentin formation.

The research presents a novel synthetic photosensitizer for photodynamic therapy (PDT) of malignant tumors - meso-tetra(3-pyridyl) bacteriochlorin, which absorbs at 747 nm (in the long-wavelength region of the spectrum) and is stable when stored in the dark. H2Py4BC demonstrates pronounced photoinduced activity in vitro against tumor cells of various genesis (IC50 varies from 21 to 68 nM for НЕр2, EJ, S37, CТ26, and LLC cultured cells) and provides in vivo pronounced antitumor efficacy in the treatment of mice bearing small or large S37, Colo26, and LLC metastatic tumors, as well as in the treatment of rats bearing RS-1 liver cholangioma. As a result, total regress of primary tumor nodules and cure of 40 to 100% of the animals were proved by the experiment criteria, MRI, and histological analysis. Meso-tetra(3-pyridyl) bacteriochlorin quickly penetrates and accumulates in the tumor tissue and internal organs of mice, and after 24 hours 80% of the dye is excreted from skin as well as 87% - 92% from liver, kidneys, and spleen.

Cancer remains one of the most critical global health issues. Conventional treatments, such as radiotherapy, surgery, or chemotherapy, have limitations, especially concerning side effects, resistance, and recurrence. Consequently, new innovative treatments to overcome these problems are needed. Photothermal therapy (PTT) is a promising alternative that uses photothermal agents that convert near-infrared light (NIR) into heat to kill cancer cells. Nanoparticles can be used as photothermal agents and also as drug delivery platforms, improving the drugs’ stability, allowing for targeted delivery, and reducing toxicity. Due to its broad absorption band, high surface area, and versatility for surface functionalization, tungsten disulfide (WS2) has high potential in this context. This paper presents the state-of-the-art on the use of WS2-based materials to achieve effective and biocompatible anti-anticancer new treatment strategies.

The rapid rise in research and development following the discovery of photodynamic therapy to establish novel photosensitizers and overcome the limitations of the technology soon after its clinical translation has given rise to a few significant milestones. These include several novel generations of photosensitizers, the widening of the scope of applications, leveraging of the offerings of nanotechnology for greater efficacy, selectivity for the disease over host tissue and cells, the advent of combination therapies with other similarly minimally invasive therapeutic technologies, the use of stimulus-responsive delivery and disease targeting, and greater penetration depth of the activation energy. Brought together, all these milestones have contributed to significant enhancement of what is still arguably a novel technology. Yet the major applications of photodynamic therapy still remain firmly located in neoplasms, from where most of the new innovations appear to launch to other areas, such as microbial, fungal, viral, acne, wet age-related macular degeneration, atherosclerosis, psoriasis, environmental sanitization, pest control, and dermatology. The core value proposition of combinations of photodynamic therapy is that they enhance the leading alternative and are proposed to overcome challenges of the leading clinical anticancer and antibacterial methods, mainly due to its inherent barriers against the emergence of resistance and its rapid development of targeted and high precision therapy. Combinations with chemotherapy and radiotherapy and demonstrated applications in mop-up surgery adventitiously promise to repurpose these top three clinical tools. This review will navigate the vast and increasing innovations that have been created so as to obviate novel areas of further innovation.

BODIPY dyes have recently raised attention as potential photosensitizers. In this work, commercial and novel photosensitizers (PSs) based on BODIPY chromophores (haloBODIPYs and orthogonal dimers strategically designed with intense bands in the blue, green or red region of the Visible spectra and high singlet oxygen production) were covalently linked to mesoporous silica nanoparticles (MSNs) further functionalized with PEG and folic acid (FA). MSNs of approximately 50 nm in size with different functional groups were synthesized to allow multiple alternatives of PS-PEG-FA decoration of their external surface. Different combinations varying the type of PS (commercial Rose Bengal, Thionine and Chlorine e6 or custom-made BODIPY-based), the linkage design and the length of PEG are detailed. All the nanosystems were physicochemically characterized (morphology, diameter, size distribution and PS loaded amount) and photophysically studied (absorption capacity, fluorescence efficiency, and singlet oxygen production) in suspension. For the most promising PS-PEG-FA silica nanoplatforms, the biocompatibility in dark conditions and the phototoxicity under suitable irradiation wavelengths (blue, green, or red) at regulated light doses (10-15 J/cm2) were compared with PSs free in solution in HeLa cells in vitro.

Antimicrobial resistance (AMR), a consequence of the ability of microorganisms, especially bacteria, to develop resistance against conventional antibiotics hampering the treatment of common infections, is recognized as one of the most imperative health threats of this century. Antibacterial photodynamic therapy (aPDT) has emerged as a promising alternative strategy, utilizing photo-sensitizers activated by light to generate reactive oxygen species (ROS) that kill pathogens without inducing resistance. In this work, we synthesized silica nanoparticles of different sizes (20 nm, 80 nm, and 250 nm) functionalized with the photosensitizer Rose Bengal (RB) and a gluconamide ligand, which targets Gram-negative bacteria, to assess their potential in aPDT. Comprehensive characterization, including dynamic light scattering (DLS) and photophysical analysis, confirmed the stability and effective singlet oxygen production of the functionalized nanoparticles. RB loading was size-dependent, decreasing with increasing nanoparticle diameter. Consequently, the largest nanoparticles (250 nm) displayed insufficient RB surface density for effective aPDT, while the smallest (20 nm) and intermediate (80 nm) particles were more promising. Bacterial assays in E. coli revealed minimal dark toxicity and significant light-activated phototoxicity for the RB-loaded nanoparticles. The addition of gluconamide notably enhanced phototoxic activity, particularly in the smallest nanoparticles (RB-G-20@SiNP), which demonstrated the highest photo-toxicity-to-cytotoxicity ratio. These findings indicate that small, gluconamide-functionalized silica nanoparticles are highly effective for targeted aPDT, offering a robust strategy to combat AMR.

Glioblastoma (GBM) is an aggressive brain cancer characterized by significant molecular and cellular heterogeneity, complicating treatment efforts. Current standard therapies, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, often fail to achieve long-term remission due to tumor recurrence and resistance. A pro-oxidant environment is in-volved in glioma progression, with oxidative stress contributing to the genetic instability that leads to gliomagenesis. However, the generation of reactive oxygen species (ROS) results in the dysregulation of antioxidant defenses in GBM cells, creating a vulnerability that can be thera-peutically exploited. Evaluating pro-oxidant therapies in brain tumors is crucial due to their po-tential to selectively target and eradicate cancer cells by exploiting the elevated oxidative stress levels inherent in these malignant cells, thereby offering a novel and effective strategy for overcoming resistance to conventional therapies. This study investigates the therapeutic potential of doxorubicin (DOX) and photodynamic therapy (PDT) with Me-ALA, focusing on their effects on redox homeostasis. Basal ROS levels and antioxidant gene expression (NFE2L2, CAT, GSR) were quantitatively assessed across GBM cell lines, revealing significant variability probably linked to genetic differences. DOX and PDT treatments, both individually and in combination, were ana-lyzed for their efficacy in inducing oxidative stress and cytotoxicity. An in silico analysis further explored the relationship between gene mutations and oxidative stress in GBM patients, providing insights into the molecular mechanisms underlying treatment responses. Our findings suggest that pro-oxidant therapies, such as DOX and PDT in combination, could selectively target GBM cells, highlighting a promising avenue for improving therapeutic outcomes in GBM.

Photodynamic therapy (PDT) is a minimally invasive treatment that elicits tumor apoptosis using laser light exclusively applied to the tumor site. IR-783, an HMC dye, impedes the proliferation of breast cancer cells, even without light. However, the mechanism by which IR-783 exerts its antiproliferative effects remains unclear. We aimed to determine the efficacy of PDT using IR-783 liposomes. A heptamethine cyanine (HMC) dye excited by long-wavelength infrared light and with high tissue permeability was used for PDT after liposomization to enhance tumor tissue accumulation. PDT was performed using IR-783 in two patients with tongue and breast cancers. IR-783 liposomes similarly inhibited cell proliferation in lung cancer cells even when not excited by light. Tumor size was markedly reduced in both cases, with no significant adverse events. Furthermore, the patient with tongue cancer exhibited improved respiratory, swallowing, and speech functions, which were attributed not only to the shrinkage of the tumor, but also to the improvement of airway narrowing. In conclusion, PDT using IR-783 liposomes effectively reduces tumor size in tongue and breast cancers.

Cervical cancer is a significant global health concern, with human papillomavirus (HPV) infection being a crucial risk factor. Photodynamic therapy (PDT) is an attractive, minimally invasive treatment for HPV-related cervical lesions, which uses photosensitizers and light to selectively de-stroy abnormal cells. We aim to provide an overview of the various sorts of dyes that are utilized in PDT for decreasing the incidence and mortality of cervical cancer. Besides, the article discusses ongoing clinical trials for PDT in low-grade squamous intraepithelial neoplasia (LSIL) and high-grade squamous intraepithelial lesions (HSIL), as well as preclinical approaches for PDT in cervical cancer using various dyes. Moreover, it highlights potential dyes for PDT, examine them in in-silico condition, their pros and cons and also the solutions for enhancing their anticancer com-patibility. We also display that PDT is a promising therapeutic strategy for the diagnosis and treatment of HPV-associated cervical lesions. Moreover, it shows that using different classes of dyes improves the anticancer effects of PDT. Finally, among all dyes which are used in PDT, Fullerene demonstrated high tendency to over expressed receptors in cervical cancer cells and seems to be a proper candidate for be used in PDT more than before, but further research is necessary to assess its long-term efficacy and safety.

This study aimed to assess the impact of different modes of laser irradiation on the bactericidal efficacy of aPDT. Dentin plates were prepared by sectioning the crown dentin of bovine teeth infected with Streptococcus sobrinus. Nine aPDTs involving the combinations of three photosensitizers (brilliant blue, BB; acid red, AR; and methylene blue, MB) and three laser irradiation modes (50 mW for 120 s, 100 mW for 60 s, and 200 mW for 30 s) were performed for each infected dentin plate, and the control group consisted of the specimens not applied with aPDT. The bactericidal effects in 10 experimental groups were evaluated (n=11) using both assays of the colony-count and adenosine triphosphate (ATP). The data obtained were analyzed using the Kruskal-Wallis test. The aPDT performed with semiconductor laser in combination with BB, AR, and MB exerted a remarkable bactericidal effect. aPDT with MB exerted a more significant bactericidal effect in the colony-count assay. The results of aPDT performed with varying irradiation times and powers but with constant irradiation energy showed no difference with AR and MB between the modes, whereas BB showed a more significant bactericidal effect when irradiated for a shorter time at a higher irradiation power.

Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Seventeen eyes with PNV that underwent half-fluence PDT with adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9–18 mm from the fovea. The <9- and 9–18-mm subfields were divided into four quadrants. Choroidal thickness in each subfield decreased significantly after half-fluence PDT (P<0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9x9-mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. In conclusion, half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

Traditional photodynamic therapy (PDT) is often limited in its efficacy by insufficient light penetration, inefficient photosensitizer energy transfer, and inadequate target tissue oxygenation. X-ray activated PDT (XPDT), using nanoparticle (NPs) photosensitizers comprised of europium-doped yttrium oxide cores encased within silica shells (Y₂O₃:Eu@SiO₂), offers the potential of overcoming most of these limitations. Aimed at maximizing the generation of reactive oxygen species (ROS), this study reports methodologies for investigation of the effects of synthesis conditions on the characteristics of Y₂O₃:Eu@SiO₂ NP. Transmission electronic microscope (TEM) revealed that the NP core diameter was linearly, positively correlated with condensation time (R2 = 0.7357, p < 0.05) and linearly, negatively correlated with urea concentration (R2 = 0.958, p < 0.05). The addition of cetyltrimethylammonium bromide (CTAB) during core synthesis demonstrated enhanced particle dispersion. Silica coating via APTES-1 and TEOS-3 conditions resulted in Y₂O₃:Eu@SiO₂ NPs that generated the highest ROS, with 8.7-fold and 8.9-fold increase respectively in relative fluorescence intensity at 8 Gy irradiation compared to a 5.2-fold increase in PBS under the same condition. In vivo evaluation using 18F-fluorothymidine positron emission tomography (18F-FLT PET) of mouse xenografts of a human prototypical cancer (ovarian) revealed a 55% reduction in tumor proliferation of radiation-sensitive CAOV3 tumors treated with Y₂O₃:Eu@SiO₂ NPs compared to a 19% reduction in tumor proliferation of radiation-resistant SKOV3 tumors on the fourth day post-treatment. Taken together, these findings suggest Y₂O₃:Eu@SiO₂ NPs can serve as effective photosensitizers for XPDT and their performance characteristics can be optimized by selecting synthesis conditions and parameters to deliver the desirable therapeutic effects, offering novel approaches to circumventing many of the limitations of conventional PDT in the treatment of cancer.

Photobiomodulation (PBM) is a procedure that uses light to modulate cellular functions and bio-logical processes. Over the past decades, PBM has gained considerable attention for its potential in various medical applications due to its non-invasive nature and minimal side effects. This narrative review article examines the existing literature on PBM, encompassing research studies, clinical trials, and technological developments. This review highlights the mechanisms of action underlying PBM, including the interaction with cellular chromophores and the activation of in-tracellular signaling pathways. The evidence from clinical trials and experimental studies to evaluate the efficacy of PBM in clinical practice is summarized with a special emphasis on der-matology. Furthermore, advancements in PBM technology, such as novel light sources and treat-ment protocols, are discussed in the context of optimizing therapeutic outcomes and improving patient care. This narrative review underscores the promising role of PBM as a non-invasive therapeutic approach with broad clinical applicability. Despite the need for further research to develop standard protocols, PBM holds great potential for addressing a wide range of medical conditions and enhancing patient outcomes in modern healthcare practice.

Millions of people use public transportation daily worldwide and frequently touch surfaces, thereby producing a reservoir of microorganisms on surfaces increasing the risk of transmission. Constant occupation makes sufficient cleaning difficult to achieve. Thus, an autonomous, perma-nent antimicrobial coating (AMC) could keep down the microbial burden on such surfaces. A photodynamic AMC was applied to frequently touched surfaces in buses. The microbial burden (colony forming units, cfu) was determined weekly and compared to equivalent surfaces in buses without AMC (references). The microbial burden ranged from 0 – 209 cfu/cm² on references and from 0 – 54 cfu/cm² on AMC. The means were 13.4 ± 29.6 cfu/cm² on references and 4.5 ± 8.4 cfu/cm² on AMC (p<0.001). The difference of microbial burden on AMC and references was al-most constant throughout the study. Considering a hygiene benchmark of 5 cfu/cm², the data yield an absolute risk reduction of 22.6 % and a relative risk reduction of 50.7 %. In conclusion, photo-dynamic AMC kept down the microbial burden, reducing the risk of transmission of microor-ganisms. AMC permanently and autonomously contributes to hygienic conditions on surfaces in public transportation. Photodynamic AMC therefore are suitable for reducing the microbial load and closing hygiene gaps in public transportation.

Metallic nanoparticles (NPs), among polymeric NPs, liposomes, micelles, quantum dots, dendrimers, or fullerenes, are becoming more and more important due to their potential use in the novel medical therapies. Titanium dioxide (titanium(IV) oxide, titania, TiO2) is an inorganic compound that owes its recent rise in scientific interest to photoactivity. After the illumination in aqueous media with UV light, TiO2 produces an array of reactive oxygen species (ROS). The capability to produce ROS and thus induce cell death has found application in the photodynamic therapy (PDT) for the treatment of a wide range of maladies, from psoriasis to cancer. Titanium dioxide NPs were studied as photosensitizing agents in the treatment of malignant tumors as well as in photodynamic inactivation of antibiotic-resistant bacteria. Both TiO2 NPs themselves, as well as their composites with other molecules, can be successfully used as photosensitizers in PDT. Moreover, various organic compounds can be grafted on TiO2 NPs, leading to hybrid materials. These nanostructures can reveal increased light absorption allowing their further use in targeted therapy in medicine. In order to improve efficient anticancer therapy, many approaches utilizing titanium dioxide were tested. The most significant studies are discussed in this review.

Photodynamic inactivation (PDI) combines the nontoxic photosensitizer (PS) and visible light to generate reactive oxygen species (ROS), which can cause oxidative damages in (on) microbial organisms. Previously, we have shown that chitosan can augment the bactericidal efficacy mediated by PDI against bacteria and Candida. In this study, we showed that the antimicrobial action of chitosan to augment PDI relates to the enlargement of cell surface destruction. The microbial cell surfaces exhibit severe irregular shapes after PDI in the presence of chitosan. Furthermore, increase in the concentrations or incubation time of chitosan significantly reduce the amounts of photosensitizers TBO required, indicating that chitosan could be a synergistic agent with PDI against human pathogens. A prolonged lag phase was found in PDI surviving microbial cells, in which chitosan can act to synergistically eradicate the cells. Once the impaired cells rebuild their cellular functions from PDI-induced damage, the increased cytotoxic effect of chitosan disappeared. Together, our results suggest that chitosan with an augmented bactericidal activity after PDI is to inhibit the rehabilitation of PDI surviving cells, leading to microbial death.

The aim of this study is to prepare redox-sensitive nanophotosensitizers for targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with β-cyclodextrin (bCD) via disulfide bond creating nanophotosensitizers that were fabricated for redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize suc-cinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss) and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). Chemical composition of bCDsu-ss-Ce6 was confirmed with 1H and 13C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by dialysis procedure. They formed small particles with an average particle size of 152.0±23.2 nm and they showed improved singlet oxygen (SO) generation in the aqueous solution under light irradiation and was significantly higher than that of Ce6 alone. Ce6 release rate from bCDsu-ss-Ce6 nanophotosensitizers was accelerated by addition of glutathione (GSH), indicating that bCDsu-ss-Ce6 nanophotosensitizers have re-dox-sensitive photosensitizer delivery capacity. bCDsu-ss-Ce6 nanophotosensitizers have low in-trinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, bCDsu-ss-Ce6 nanophotosensitizers showed improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production and phototoxicity compared to those of Ce6 alone. GSH addition resulted in higher Ce6 uptake ratio, ROS generation and phototoxicity than those of Ce6 alone, indicating that bCDsu-ss-Ce6 nanophotosensitizers have redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. At tumor xenograft model using HeLa cells, bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than normal organs, i.e. fluores-cence intensity in tumor tissues was significantly higher than those of other organs while Ce6 alone did not specifically target tumor tissue. These results indicated higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, by efficiently inhibiting growth of tumor in in vivo animal tumor xenograft study.

A Pacific brittle star Ophiura sarsii has previously been shown to produce a chlorin (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) (1) with potent phototoxic activities making it applicable to photodynamic therapy. Using extensive LC-MS metabolite profiling, molecular network analysis and targeted isolation with de novo NMR structure elucidation, we here identify five additional chlorin compounds from O. sarsii and its deep-sea relative O. ooplax: 10S-Hydroxypheophorbide a (2), Pheophorbide a (3), Pyropheophorbide a (4), (3S,4S,21R)-14-Ethyl-9-(hydroxymethyl)-21-(methoxycarbonyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (5), and (3S,4S,21R)-14-Ethyl-21-hydroxy-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (6). Chlorins 5 and 6 have not been previously reported in natural sources. Interestingly, low amounts of chlorins 1-4 and 6 could also be identified in a distant species, the basket star Gorgonocephalus cf. eucnemis, demonstrating that chlorins are produced by a wide spectrum of marine invertebrates of the class Ophiuroidea. Following purification of these major Ophiura chlorin metabolites, we discovered the high singlet oxygen quantum yield upon their photoinduction and their strong phototoxicity against a panel of cancer cell lines. These studies identify an arsenal of brittle star chlorins as powerful natural photosensitizers with potential photodynamic therapy applications.

The increasing popularity of porphyrins and hydroporphyrins for application in a variety of biomedical (photodynamic therapy, fluorescence tagging and imaging, photoacoustic imaging) and technical (chemosensing, catalysis, light harvesting) applications is also associated with the growing number of methodologies that enable their solubilization in aqueous media. Natively, the vast majority of synthetic porphyrinic compounds are not water-soluble. Moreover, any water-solubility imposes several restrictions on the synthetic chemist on when to install solubilizing groups in the synthetic sequence, and how to isolate and purify these compounds. This review summarizes the chemical modifications to render synthetic porphyrins water-soluble, with a focus on the work since 2000. Where available, practical data such as solubility, indicators for the degree of aggregation, and special notes for the practicioner are listed. We hope that this review will guide synthetic chemists through the many strategies known to make porphyrins and hydroporphyrins water soluble.

Treatment regimens are regularly evolving, together with novel therapies and drugs. Such evolution is necessary to circumvent resistance mechanisms and to give patients the best possible health care. When dealing with cancer, most regimens involve multiple treatments (surgery, radiation therapy, chemotherapy, immunotherapy, etc.). The purpose of this study was to associate in a single compound metal-based drugs and photosensitizers to combine chemotherapy and photodynamic therapy. Two arene-ruthenium tetrapyridylporphyrin compounds (2H-TPyP-arene-Ru and Zn-TPyP-arene-Ru) have been synthesized and evaluated on two colorectal cancer cell lines (HCT116 and HT-29). The cytotoxicity and phototoxicity have been evaluated. In addition, the anticancer mechanism and the cell death process mediated by the two compounds were studied. The results showed that the two arene-ruthenium photosensitizer-containing complexes have a strong phototoxic effect after photoactivation. The 2H-TPyP-arene-Ru induced outstanding cytotoxicity when compared to the Zn-TPyP-arene-Ru analogue. Moreover, under light, these two arene-ruthenium photosensitizers induce an apoptotic process in human colorectal cancer cell lines.

Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract Orthoquin^TM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner, across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or pre-mature release of viral genomes as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.

The kinetics and optimal efficacy conditions of photoinitiated polymerization are theoretically presented. Analytic formulas are derived for the crosslink time, crosslink depth and efficacy function. The roles of photosensitizer (PS) concentration, diffusion depth and light intensity on the polymerization spatial and temporal profiles, for both uniform and non-uniform cases, are presented . For optimal efficacy, a strategy via controlled PS concentration is proposed, where re-supply of PS in high light intensity may achieve a combined-efficacy similar to low light intensity, but has a much faster procedure. A new criterion of efficacy based on the polymerization (crosslink) [strength] and [depth] is introduced.

Age related macular degeneration (AMD) as the name suggest is the timely degradation of the macular area of the eye which can lead to vision impairment, in particular the central vision. Macular is one of the important areas of the eye, present in the retina which controls our central vision. AMD is one of the most common types of irreversible blindness caused in older population of the society in developed countries. AMD is broadly classified as Dry AMD (Non Neovascular AMD) and Wet AMD (Neovascular AMD). Non Neovascular AMD more commonly known as Dry AMD is less aggressive and is very frequent type of AMD caused, it has three stages 1) Early dry AMD, 2) Intermediate Dry AMD, and 3) Late AMD. One the several therapies used to treat AMD is stem cells where Induced pluripotent stem cells (IPSC’s) derived retinal pigment epithelium (RPE) cells was used to treat dry AMD. The use of siRNA that targets Vascular endothelial growth factor (VEGF-A) using different nanotechnology-based delivery system like the organic nanoparticles synthesized liposomes. An upcoming therapy used most widely in recent times is the photodynamic therapy where a photodynamic drug like verteporfin which a benzoporphyrin derivative is used, where the outcome shows great promise in reducing vision loss in wet AMD. This review discusses in details about age related macular degeneration and also its different novel therapies that is been currently used extensively.

Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.

The spread of multidrug-resistant mycobacterium strains requires the development of new approaches to combat diseases caused by these pathogens. For that, photodynamic inactivation (PDI) is a promising approach. In this study, a tricarbocyanine (TCC) is used for the first time as a near-infrared (740 nm) activatable PDI photosensitizer to kill mycobacteria with deeper light penetration. For better targeting, a novel tricarbocyanine dye functionalized with two trehalose units (TCC2Tre) is developed. The photodynamic effect of the conjugate against mycobacteria, including Mycobacterium tuberculosis, is evaluated. Under irradiation, TCC2Tre causes more effective killing of mycobacteria compared to the photosensitizer without trehalose conjugation, with 99.99% dead vegetative cells of M. tuberculosis and M. smegmatis. In addition, effective photoinactivation of dormant forms of M. smegmatis is observed after incubation with TCC2Tre. Mycobacteria treated with TCC2Tre are more sensitive to 740 nm light than the Gram-positive Micrococcus luteus and the Gram-negative Escherichia coli. For the first time, this study demonstrates the possibility of in vitro PDI of mycobacteria including the fast-growing M. smegmatis and the slow-growing M. tuberculosis using near-infrared activatable photosensitizers. These findings are useful for the development of new efficient alternatives to antibiotic therapy.

Microbial diseases have been declared one of the main threats to humanity, which is why, in recent years, great interest has been generated in the development of nanocomposites with antimicrobial capacity. In the present work, two magnetic nanocomposites, based on Graphene Oxide (GO) and Multiwall Carbon Nanotubes (MWCNTs) were studied. The synthesis of these magnetic nanocomposites consisted of three phases: first, the synthesis of Iron Magnetic Nanoparticles (MNPs) was carried out in the presence of MWCNTs and GO using the Co-precipitation method. The second phase consisted of the adsorption of photosensitizer menthol-Zinc phthalocyanine (ZnMintPc) into MWCNTs and GO, and the third phase was the encapsulation in poly (N-vinylcaprolactam-co-poly(ethylene glycol diacrylate)) poly (VCL-co-PEGDA) polymer VCL/PEGDA a biocompatible hydrogel, in order to obtain the magnetic nanocomposites: VCL/PEGDA-MNPs-MWCNTs-ZnMintPc and VCL/PEGDA-MNPs-GO-ZnMintPc. In vitro studies were carried out using Escherichia coli and Staphylococcus aureus bacteria and the Candida albicans yeast based on the PTT/PDT effect. This research describes the optical, morphological, magnetic and photophysical characterizations of nanocomposites and their application as antimicrobial agents. It was evaluated the antimicrobial effect of magnetics nanocomposites based on the Photodynamic/Photothermal (PDT/PTT) effect; for this purpose, doses of 65 mW cm-2 at 630 nm of light were used. The VCL/PEGDA-MNPs-GO-ZnMintPc nanocomposite was able to eliminate colonies of E. coli and S. aureus, while VCL/PEGDA-MNPs-MWCNTs-ZnMintPc nanocomposite was able to eliminate the three types of microorganisms; consequently, the latter is considered a broad-spectrum of antimicrobial agent in PDT and PTT.

The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its selective conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently marketed drugs - the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat - that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial.

Gold nanoparticles (NPs) have demonstrated significance in several important fields, including drug delivery and anticancer research, due to their unique properties. Gold NPs possess significant optical characteristics that enhance their application in biosensor development for diagnosis, photothermal and photodynamic therapies for anticancer treatment, as well as in targeted drug delivery and bioimaging. The broad surface modification possibilities of gold NPs have been utilized in the delivery of various molecules, including nucleic acids, drugs, and proteins. Moreover, gold NPs possess strong localized surface plasmon resonance (LSPR) properties, facilitating their use in surface-enhanced Raman scattering for precise and efficient biomolecule detection. These optical properties are extensively utilized in anticancer research. Both photothermal and photodynamic therapies show significant results in anticancer treatments using gold NPs. Additionally, the properties of gold NPs demonstrate potential in other biological areas, particularly in antimicrobial activity. In addition to delivering antigens, peptides, and antibiotics to enhance antimicrobial activity, gold NPs can penetrate cell membranes and induce apoptosis through various intracellular mechanisms. Among other types of metal NPs, gold NPs show more tolerable toxicity capacity, supporting their application in wide-ranging areas. Gold NPs hold a special position in nanomaterial research, offering limited toxicity and unique properties. This review aims to address recently highlighted applications, current status of gold NP research and discuss their future in nanomedicine.

Porphyrinic photosensitizers (PSs) and their nano-sized polymer-based carrier systems are required to exhibit low dark toxicity, avoid side effects, and ensure high in vivo tolerability. Yet, little is known about the intracellular fate of PSs during the dark incubation period and how it is af-fected by nanoparticles. In a systematic study, high resolution magic angle spinning NMR spectroscopy combined with statistical analyses was used to study the metabolic profile of cultured HeLa cells treated with different concentrations of the PS chlorin e4 (Ce4) alone or encapsulated in carrier systems. For the latter, either polyvinylpyrrolidone (PVP) or the micelle forming polyethylene glycol (PEG)-polypropylene glycol triblock copolymer Kolliphor P188 (KP) were used. Diffusion edited spectra indicated Ce4 membrane localization evidenced by Ce4 concentration dependent chemical shift perturbation of the cellular phospholipid choline resonance. The effect was also visible in the presence of KP and PVP, but less pronounced. The appearance of the PEG resonance in the cell spectra pointed towards cell internalization of KP whereas no conclusion could be drawn for PVP that remained NMR-invisible. Multivariate statistical analyses of the cell spectra (PCA, PLS-DA and oPLS) revealed a concentration-dependent metabolic response upon exposure to Ce4 that was attenuated by KP and even more by PVP. Significant Ce4-concentration dependent alterations were mainly found for metabolites involved in the tricarboxylic acid cycle and the phosphatidylcholine metabolism. The data underline an important protective role of the polymeric carriers following cell internalization. Moreover, the current study allowed - to our knowledge for the first time - to trace the intracellular PS localization on an atomic level by NMR methods.

Collagen has been accepted in drug delivery structures due to its biocompatible chemical, physicochemical and curative actions. The study aims to evaluate the effects of a bovine collagen hydrolysate (Clg) on the main photophysical and photodynamic properties of a new gallium (III) phthalocyanine (GaPc). The absorbance of GaPc and the conjugate GaPc-Clg showed a decrease of the intensive Q-band (681 nm) and a blue shift of the maximum (678 nm) with loss of UV-band (354 nm) for 40 mg/mL Clg. The fluorescence of GaPc was evaluated with strong emission peak at 694 nm (exc: 615 nm) which was lower for GaPc-Clg (691 nm). The quantum yield of 0.23 was obtained for GaPc which was reduced for GaPc-Clg (0.012). Photo- and dark cytotoxicity was studied by NRU-assay on pigmented melanoma cells (SH-4) and normal cell lines (BJ and HaCaT). The results suggested a slight reduction of cytotoxicity for the conjugate but almost double for the selectivity index (SI: 0.71 vs. 1.49 for HaCaT cells). The study showed that bovine collagen hydrolysate can lower the PDT activity of a powerful photosensitizer with phototherapeutic index: 819 to 360, but also minimized its dark toxicity as a positive effect in the photodynamic treatment.

The design of more efficient photosensitizers is a matter of great importance in the field of cancer treatment by means of photodynamic therapy. One of the main processes involved in the activation of apoptosis in cancer cells is the oxidative stress on DNA once a photosensitizer is excited by light. As a consequence, it is a matter of great relevance to investigate in detail the binding modes of the chromophore with DNA, and the nature of the electronically excited states that participate in the induction of DNA damage, for example, charge-transfer states. In this work, we investigate the electronic structure of the anthraquinone photosensitizer intercalated into a double-stranded poly(dG-dC) decamer model of DNA. First, the different geometric configurations are analyzed by means of classical molecular dynamics simulations. Then, the excited states for the most relevant poses of anthraquinone inside the binding pocket are computed by an electrostatic-embedding quantum mechanics/molecular mechanics approach, where anthraquinone and one of the nearby guanine residues are described quantum mechanically to take into account intermolecular charge-transfer states. The excited states are characterized as monomer, exciton, excimer and charge-transfer states based on the analysis of the transition density matrix, and each of these contributions to the total density of states and absorption spectrum is discussed in terms of the stacking interactions. These results are relevant as they represent the footing for future studies on the reactivity of anthraquinone derivatives with DNA and give insights on possible geometrical configurations that potentially favor the oxidative stress of DNA.

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. Being composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module looks advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering. Both new MNTs demonstrated high affinity for target receptors, as revealed by fluorescently labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNT. Thus, this work reveals that MNT’s carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1.

Within this work we review the metal coordination effect on the photophysics of metal dipyrrinato complexes. Dipyrrinato complexes are promising candidates in the search for alternative transition metal photosensitizers for application in photodynamic therapy (PDT). These complexes can be activated by irradiation with light of a specific wavelength, after which cytotoxic reactive oxygen species (ROS) are generated. The metal coordination allows for the use of the heavy atom effect, which can enhance the triplet generation necessary for generation of ROS. Additionally, the flexibility of these complexes for metal ions, substitutions and ligands allows the possibility to tune their photophysical properties. A general overview of the mechanism of photodynamic therapy and the properties of the triplet photosensitizers is given, followed by further details of dipyrrinato complexes described in the literature that show relevance as photosensitizers for PDT. In particular, the photophysical properties of Re(I), Ru(II), Ir(III), Ni(II), Cu(II), Pd(II), Pt(II), Zn(II), Ga(III), In(III), Al(III), Sn(II), and P dipyrrinato complexes are discussed. The potential for future development in the field of (dipyrrinato)metal complexes is addressed and several new research topics are suggested throughout this work. We propose that significant advances could be made for heteroleptic bis(dipyrrinato)zinc(II) and homoleptic bis(dipyrrinato)palladium(II) complexes and their application as photosensitizers for PDT.

The World Health Organization (WHO) cancer agency predicts that more than 35 mil-lion cases of will be experienced in 2050, a 77 % increase over the 2022 estimate. Cur-rently, the leading cancer diagnosed cancer are breast, lung and colorectal. There is no standardized tool for cancer diagnosis; initially clinical procedures are guided by the patient´s symptoms and generally involve biochemical blood tests, imaging and biopsy. Label-free nonlinear optical approaches are promising tool for tumor imaging, due to their inherent non-invasive biosafe contrast mechanisms and the ability to monitor collagen-related disorders and metabolic changes during cancer progression. Last ad-vances in nonlinear modalities for tumor imaging are reviewed here. In addition, an application of a blind deconvolution procedure to improve the quality of two-photon images of breast tumor tissues is shown.