1. Introduction
Bacterial infections and related antimicrobial resistance are under World health Organisation (WHO) and Centers of Disease Control and Prevention (CDC) surveillance worldwide,[
1] in all healthcare sectors and agriculture,[
2] due to the increased morbidity and mortality caused.[
3] Increasing antimicrobial resistance is one of the top ten “global public health threats facing humanity”, [
4,
5] thus impacting individuals at every stage of life, personal, professional levels or societal.[
6,
7] Bacteria are harmful to humans directly through the resistance to commonly used antibiotics [
8] or the resulting severe adverse effects induced by the second and third-line treatments of nosocomial infections, primarly antibiotic-resistant infections.[
4,
6,
9,
10,
11,
12,
13] One of the most pressing challenges is to define new antibacterial materials and strategies with high efficiency, safety, and convenience,[
14] knowing that traditional drugs or methods failed due to drug resistance.[
15,
16] Nanotechnology-based delivery systems and engineered nanoparticles developed as alternative “nanoantibiotics”.[
17] Nanoparticles (NPs) demonstrated the most effective method to address multi-drug-resistant bacteria since they not only act as transporters for natural antibiotics and antimicrobials but also actively combat bacteria. Inorganic NPs (e.g., silver (Ag), [
18,
19,
20,
21] zinc oxide (ZnO) [
22,
23,
24], gold (Au) [
25,
26,
27], titanium oxide TiO
2 [
28], copper (Cu)[
29], copper oxide (CuO) [
30], Nickel (Ni), [
31] selenium (Se)),[
32] and natural and synthetic organic NPs (e.g., liposomes, polymeric nanoparticles, micelles, ferritin), [
33,
34] can be used alone or as nanocarriers for therapeutic molecules (e.g., liposomes, polymeric NPs, and dendrimers).[
35,
36] Hybrid NPs combine organic and inorganic NPs in the same composite system.[
37] Nanomaterials were used as antibacterial agents, and dynamic therapies were designed for better efficacy by increasing drugs’ bioavailability, targeted distribution, and decreasing toxicity.[
38,
39,
40] Notably, the nanomaterials’ physical and chemical properties (dimension under 100 nm, morphology, crystal structure, defect state, surface energy, surface potential) can be tuned to meet the requirements of specific applications.[
41,
42] Moreover, stimulus-based tuneable noninvasive approaches include dynamic therapy, which employs various stimuli such as thermal (photothermal therapy),[
43] chemical or electrical [
44] (photodynamic therapy - PDT), immunotherapy,[
45] and gene therapy, each of them with their advantages and limitations.[
17,
46,
47] In the case of localised surface plasmon resonance (LSPR) by photothermally active nanomaterials (photothermal agents - PTAs), the absorbed energy (near-infrared -NIR- light, 700-1300 nm) is released as heat (hyperthermia up to 90
°C). It alters the membrane, inactivates proteins, and releases intracellular material for
in situ-fine-tuning photothermal ablation of bacteria or even damaging surrounding cells.[
46] The photothermal effect, in range with the
biological transparency window,[
48] allows deep penetration of light (up to 1cm) into infected tissue,[
49] avoids mutations in the targeted bacteria and kills planktonic multidrug-resistant (MDR) microorganisms and biofilm. However, the short and long-term biological concerns restricting PTT applications imposed PTAs functionalisation for specific bacteria, moving towards lower-energy (i.e.., NIR-II 1000–1700 nm, and NIR-III 1800–2100 nm) or active photothermal materials for multimodal synergistic-based therapies to minimize side effects and maintain low cost (i.e., PTT-PDT, PTT- CDT, PTT-photocatalytic, PTT-immunotherapy, PTT-catalytic).[
50,
51]
Here, we review the recent achievements and current trends in developing photothermally active nanostructures, including plasmonic metals, semiconductor, carbon-based, and organic photothermal polymers, and antibacterial mechanisms of action (MOA), including anti-MDR bacteria and biofilms removal. Also, new non-conventional photothermal-based antimicrobial systems with remarkable synergistic effects are presented. Most relevant PTAs applications are reviewed, such as anti-biofilm formation, biofilm penetration or ablation, and nanomaterial-based infected wound therapy. We overview the strength, limitations, and general challenges of photothermal treatment using nanomaterials to highlight the research directions.
3. Photothermal antimicrobials agents
Metals (such as Au, Cu, Pd, Bi), semiconductors oxide (WO3, Fe3O4), semiconductors chalcogenides or dichalcogenides (CuS, MoS2, NiS2, SnSe, CuSe), mettaloids (B) and nonmetals (C, P) are inorganic nanostructures that absorb energy strongly in the NIR region.
Metal-based NPs are at the forefront of fighting bacteria as” light-directed nanoheaters” due to their substantial light-to-heat conversion efficiency. Recent achievements focused on developing plasmonic metals have boosted their applications in antimicrobial applications. Plasmonic metal NPs can express an effective and targeted antibacterial activity against a broad spectrum of bacterial strains.
The most used plasmonic metal for bacteria photothermolysis is Au in different shapes, sizes, and structures. The representative Au-based PTAs, and other inorganic nanomaterials and their antibacterial activities are presented in
Table 1. Nano-gold (nanorods, nanostars, nanobipyramids, nanowires, nanoworms, nanoflowers) present fascinating localised surface plasmonic resonance (LSPR) properties while the chemical inertness that makes gold nanostructures suitable for bacteria ablation through photoinduced hyperthermia. Au NPs have been widely adopted for biological applications due to their easy nanoscale fabrication and high oxidation and degeneration resistance.[
57] Controlling the shape and size of Au nanostructures, optically tuned the LSPR activity, at different light wavelengths, from visible to the NIR region.[
58,
59] Using Au NPs for bacterial photothermal ablation is an evolving application, from the first
in vitro study using bioconjugated Au plasmonic NPs under laser light [
60] to the proof of principle of PTT biofilm removing [
61] and Au nanostructures involved in PTT bacteria ablation.[
62,
63] Au nanorods (Au NRs) were the most utilised because of their longitudinal surface plasmon resonances under NIR laser illumination. In the case of Au NRs, the photothermal bacteria ablation efficiency depends on the Au nanocrystals’ shape, size, overall structure, and, most importantly, their facets. Yougbare
et al. compared Au NRs with the (200) plane and Au nanobipyramids (Au NBPs) with the (111) plane and found that the photothermal activity of Au NBPs (111) was better against
E. coli due to easy desorbed water on the Au NBPs (111) surface for PTT hyperthermia.[
64] However, the pulsed laser irradiation induces structural damage and shape modification on Au NRs.[
65,
66] imposing additional treatment to improve structural stability under laser treatment.[
40] For instance, covering the anisotropic Au nanomaterials with polydopamine to synthesise Au nanoworms resulted in stability after seven cycles of laser irradiation, efficient antibacterial activity, and good biocompatibility.[
67] Furthermore, various species of ligands can be anchored on the AuNPs surface for surface modification of AuNPs to improve the photothermal antibacterial treatment. For example, Hu
et al. [
68] coated the Au NPs with a pH-responsive mixed charged zwitterionic layer for a good dispersion in the biological environment (pH ~7.4), excellent adherence to negatively charged methicillin-resistant
S. aureus bacteria surfaces (pH ~5.5), and increased PTT performance. Similarly, the pH-responsive surface charge transition activities functionalised the Au NRs using polymethacrylate with pendant carboxyl betaine groups.[
69] The hydrophobic/hydrophobic functionalisation of Au NRs substantially improved the antimicrobial efficiency promoting membrane disintegration. Hydrophilic functionalised polyethylene glycol (PEG)-Au NRs and hydrophobic functionalised polystyrene (PS)-Au NRs showed efficient bactericidal effects on
S. aureus and Propionibacterium acnes (P. acnes) strains: the viable bacterial count reduced from ≤85% to ≥99.99% after exposure to NIR.[
70] Other attempts to functionalise Au NRs consisted in (1) conjugating Au NRs with poly(2-lactobionamidoethyl methacrylate) and poly(2-fucose ethyl methacrylate) to specifically block bacterial LecA and LecB lectins of
P. aeruginosa who mediate biofilm formation.[
71]
In vivo, experiments showed a fast temperature increase up to 60 °C and the removal of most bacteria from the infected tissue. Protease (bromelain)-conjugated Au NRs were also used to achieve rapid biofilm thermal degradation and advanced removal of exotoxins and auto-induced peptides. Enhanced enzymatic activity of bromelain against Gram-positive and Gram-negative bacteria upon NIR laser irradiation was observed. It was regulated within 30–60°C by the laser power adjustment.[
72] Peptide and neuropeptide functionalised the surface of Au NRs through electrostatic interactions for targeted methicillin-resistant
S.aureus and
E. Coli binding and higher bactericidal activity than unconjugated Au NRs.[
73] The functionalised photothermal materials were also stable for up to four cycles of NIR laser irradiation.
Silver (Ag), like Au, exhibits strong plasmonic properties in the visible region, where biological tissues absorb. Merkl
et al. [
74] obtained Ag plasmonic fractal-like nanoaggregates with tuneable extinction from visible to NIR wavelengths. Using SiO
2 during the flame synthesis of the spherical Ag NPs a dielectric spacer was created between plasmonic Ag NPs to tune plasmonic coupling, prevent any potential dissolution of Ag, and inhibit nanostructures’ sintering or restructuring. The resulting nanomaterial was incorporated into a polymer layer and used as photothermal coatings on medical devices. Continuous laser irradiation at 808 nm completely eradicated
E. coli biofilms after 5 min and
S. aureus after 10 min. Interestingly, as Ag dissolves in biological media and hyperthermia accelerates the process and consumes the photothermal agent during PTT, Ag NPs-embedded hydrogel releases Ag
+, acting as PTA for antimicrobial PTT under a NIR laser.[
75] Thus, nanostructures with plasmonic properties should be engineeringly changed to absorb in the NIR regions and be used in wound healing.[
76,
77,
78]
Copper (Cu) alone is highly oxidised. Therefore, nanoCu can act as a nanoenzyme[
79] with high photothermal conversion efficiency as it undergoes Fenton-like reactions in a wide pH range. Notably, the atomically dispersed Cu ensured the photothermal properties and significantly improved the catalytic performance of Cu single-atom sites/N doped porous carbon (Cu SASs/NPC), which showed 100% antibacterial efficiency against
E. coli and
MRSA through photothermal-catalytic antibacterial treatment.[
80] Furthermore, Cu SASs/NPC demonstrated good photothermal stability due to the particular structural configuration.
Palladium (Pd), used for photothermal cancer therapy, exhibits good photothermal stability and high optical extinction coefficients useful in bacterial photothermolysis. Recently, biocompatible PdNPs prepared via Bacillus megaterium Y-4 and biologically reduced and ultrasonically treated [
81] presented improved photothermal conversion and bacterial ablation at low doses through an improved absorption in the NIR region.
Bismuth (Bi)-based nanomaterials with a bandgap of less than 1.53 eV can absorb in the NIR range. Pristine Bi, Bi-based compound nanomaterials and composites also expressed antibacterial PTT and PDT capabilities,[
82] thus having the potential to treat bacterial infections. However, Bi oxidizes during irradiation, so strategies must be implemented to prevent this phenomenon and increase the Bi biomedical applications.
Bimetallic plasmonics. The chemical stability of Ag can be improved by debasing with Au to expand overall functionality.
Ag /Au bimetallic NPs were synthesized onto a jellyfish-based scaffold. This antibacterial material can actively and spontaneously reduce Ag and Au ions and form NPs directly on the nanofibers’ surface due to Q-mucin glycoproteins’ presence in nanofibers.[
83] The heat generated by small plasmonic NPs is more significant than the heat from the bigger and scattered NPs. The resulting materials proved to have combined actions against bacterial biofilm: disrupt/remove bacterial colonies and mature biofilms and prevent their regrowth. Another way to preserve the stable shapes of Ag NPs is to frame them with a more stable metal. Zhang
et al. [
76] proposed another type of architecture of AuAg yolk−shell cubic nanoframes with the nanosphere as the core and the cubic nanoframe as the outer shell. The existence of a void between the core and the shell parts came with some advantages, such as multiple reflections of the incident light between the shell and the core parts and an extensive electromagnetic field interaction between these unconnected parts. The material depolarises the bacterial membrane and affects the membrane potential, and the NIR laser exposure further increases the initial effect. TEM images of exposed
MRSA showed leakage of intracellular substances.
Pd-Cu nanoalloy, in combination with amoxicilli and encapsulated in zeolitic imidazolate framework-8, formed a complex antimicrobial system.[
84] The photothermal nanoalloy significantly stimulates drug release, has good biocompatibility and has a significant antibacterial effect on planktonic bacteria and their biofilms.
Metallic compounds-based PTAs
Metal sulfides, oxides, selenides, and carbides, with lower cost than noble metals, are also used as PTAs due to their large surface area and facile surface modification. The nanomaterials have high photothermal conversion efficiency provided by the large band gap.
Copper sulfide (CuS) NPs transform light to heat due to the d–d transition of Cu
2+, and the maximum absorption peak cannot be shifted by changing the particle morphology. In practice, an NIR laser at 980 nm is used because some Cu-based nanomaterials need a high-powered NIR laser at 808 nm. The antimicrobial performance of CuS nanosheets via synergistic photothermal and photodynamic mechanisms depends on sulfur vacancies (Vs) concentration.[
85] In the case of CuS, the CuS nanosheets with the highest Vs concentration achieved bactericidal rates of 99.9% against
Bacillus subtilis and
E. coli bacteria under 808 nm laser irradiation. The photothermal conversion efficiency was 41.8%. Similar results were obtained for other defect-rich CuS [
86]. Recently, Chan
et al. proposed a multifunctional platform (HNTs@CuS@PDA-Lys) to treat bacterial infections by synergistic lysozyme (Lys)-photothermal therapy.[
87] The complex platform includes halloysite nanotubes (HNT), a natural clay mineral decorated with CuS, and a polydopamine (PDA) coating functionalised with antimicrobial enzyme Lys. HNTs@CuS@PDA-Lys exhibited excellent bactericidal activity against
E. coli (100.0 ± 0.2 %) and
S. aureus (99.9 ± 0.1 %), eliminating 75.9 ± 2.0 % of
S. aureus biofilm under NIR irradiation (808 nm, 1.5 W/cm
2). Under NIR light exposure, a synthesised heterojunction composite of graphdiyne nanowalls wrapped hollow copper sulfide nanocubes (CuS@GDY) also presented strong localised surface plasmonic resonance and enzyme mimic function.[
79] The nanocomposite acts through the combined hyperthermic and increased peroxidase-like activities, facilitated by the exclusive hierarchical configuration, the tight bandgap of GDY nanowalls, LSPR effect of CuS nanocages, fast interfacial electron transfer dynamics, and carbon Vs on CuS@GDY. Also, Cu
7S
4-2 with (224) facets showed outstanding antibacterial efficiency against
B. subtilis,
E. coli and drug-resistant
P. aeruginosa compared with Cu
7S
4-1 with (304) exposed facets via synergetic PDT and PTT.[
86]
Molybdenum disulfide (MoS
2) belongs to the category of two-dimensional transition metal dichalcogenide nanosheets. Recently, its electronic structure was modulated by Vs engineering, with different concentrations of sulfur vacancies (Vs) being generated to optimize photothermal conversion efficiency. This strategy improves light absorption and avoids the recombination of photogenerated electrons-hols pairs. MoS
2 with abundant vacancy strongly binds to bacteria inhibiting colony formation. Above a specific concentration, excessive Vs on the surface of MoS
2 can be responsible for charge carriers blocking and photothermal performance decrease.[
88,
89] The photothermal conversion efficiency (η) was 45.97%, and bacteria were eliminated under the 808 nm NIR light irradiation. In another study, MoS
2 nanosheets were doped with copper ions (MoS
2@Cu2+) for reduced electron–hole recombination and improved photothermal efficiency.[
90]
A biodegradable multifunctional
nickel sulfide (NiS
2) nanozymes with photothermal performance, nano-catalysis property, and glutathione (GSH)- depleting function was proposed in [
91]. This nanomaterial showed very good photothermal performance, catalytic properties, good stability, and rapid metabolism, proving a peroxidase-like ability to kill bacteria.
Biogenic
copper selenide NPs (bio-CuSe) were incorporated in a polyvinylidene fluoride membrane to improve its qualities and antimicrobial properties. [
92] NIR irradiation increased water temperature near the membrane, allowing for > 95% suppression of bacterial growth. The obtained conversion efficiency was 30.8%.
Tin selenides (SnSe) with different morphologies (sphere, rod, plate, and surface wrinkled) were investigated as PTAs. Spherical SnSe showed the best antimicrobial performance through combined photothermal and photodynamic mechanisms that managed to eliminate 99.99% of
E. coli and
B. subtilis bacteria.[
93] The best calculated photothermal conversion efficiency was 41.4%, higher than other published values.
Ferrous-ferric oxide (Fe
3O
4) NPs have a strong enzyme-like catalytic ability in a wide pH range and can be used in a photothermal-enzymes combined antibacterial treatment platform. The photothermal effect can increase production of •OH from H
2O
2 through the Fenton reaction. Interestingly, the catalytic activity of Fe
3O
4 NPs intensifies with increasing temperature in the range of 25–50°C.[
94]
In vitro wound treatment with NIR laser after adding H
2O
2 damaged the biofilm. Also, the combined treatments showed less wound inflammation after in
vivo tests. Lv
et al. synthesised magneto-plasmonic multi-branched Fe
3O
4@Au core@shell nanocomposites [
95] with a photothermal conversion efficiency of 69.9%, a complete bacteria ablation after NIR irradiation, good photo-stability and several times repeated use.
MXene materials, bidimensional transitional metal carbide/nitride, have gained increased attention since their discovery in 2011.[
52] MXenes exhibit hydrophilicity and outstanding photothermal-conversion efficiency, which can lead to good antimicrobial activity.[
96] Very recently, MXene were tested for antimicrobial applications and the results were unsatisfactory due to poor MXene-bacteria interactions and bacterial rebound
in vivo. Ti
3C
2MXene was then used in a photothermal treatment and proved to have a unique membrane-disruption effect, with sharp edges of nanosheets acting as “nanoknives”.[
97] Different strategies were tried to improve antimicrobial efficiency. In [
98], lysozyme was immobilized on titanium carbide Ti
3C
2TX MXene ultra-thin nanosheets modified with polydopamine for light-enhanced enzymatic inactivation of antibiotic-resistance bacteria due to close contact between this antimicrobial material and bacteria. In another study, Ti
3C
2TX MXene were combined with ciprofloxacin and incorporated in a hydrogel to trap and kill all the tested bacteria effectively.[
99] An engineered interface between n-type Bi
2S
3 nanorods and Ti
3C
2Tx nanosheets produced more ROS due to the accelerated photogenerated charge separation and transfer due to the differences between their work function values. Bi
2S
3 NR grew directly on the surface of Ti
3C
2Tx nanosheets leading to the generation of a potential contact difference and an increase in the local electron density on Ti
3C
2Tx, reducing the recombination of the electron-hole pairs. This nanocomposite was a stable, biocompatible, highly effective antimicrobial with enhanced photocatalytic and photothermal properties.[
100]
Other inorganic PTAs
Black phosphorus (BP) is a layered two-dimensional (2D) semiconductor material applied as a photothermal agent due to its high photothermal conversion efficiency, extinction coefficient, biocompatibility, and excellent biodegradability.[
101] BP exhibits less cytotoxicity than graphene, still being more toxic compared to other 2D nanomaterials.[
102] Even without NIR irradiation, BP nanosheets can cause physical damage to the bacterial membrane, RNA leakage, and death because of the sharp edges of the sheets.[
103] As a disadvantage, BP nanosheets can undergo rapid oxidation and degradation in ambient environments.[
104] The photothermal conversion efficiency of BP nanosheets can be further enhanced by conjugation with Au. This nanocomposite can destroy up to 58% of Enterococcus faecalis bacteria from the biofilm under NIR light irradiation.[
105] BP nanosheets decorated with cationic carbon dots (CDs) acted against bacteria through photothermal, photodynamic therapy, and electrostatic interactions between cationic CDs and bacteria walls.[
106] CuS NPs were immobilized onto BP nanosheets resulting in an efficient synergistic nanocomposite for fighting
P. aeruginosa and
S. aureus cells.[
107] After a few minutes of NIR irradiation, the temperature rises by 30.4 ◦C due to the photothermal conversion efficiency of both CuS and BP nanosheets. Recently, Zhao
et al. [
108] fabricated antibacterial photothermal nanofibres composed of polycaprolactone (PCL), Ag NPs and BP for infected wound healing. After irradiation, a significant increase in temperature was registered up to 41°C generated by the BP, and this hyperthermia accelerates the movement of Ag+, avoiding the formation of silver aggregates. The
in vivo studies indicated that the application of these complex nanofibres accelerated wound healing. Other studies proposed the conjugation of the two nanomaterials - BP and Ag NPs - in a BP@AgNPs nanohybrids with broadened visible light absorption [
77] or a BP/Ag NPs nanocomposite [
109] with higher efficiency for Gram-positive bacteria than Gram-negative bacteria.
Amorphous
red phosphorus (RP) has rarely been applied despite its good biocompatibility. In one study, RP was used in a layered composite (with a graphene oxide layer on top), showing rapid and almost complete microbial inactivation under visible and NIR light.[
110]
Boron. A multifunctional nanoplatform based on boron nanosheet (B NS)-coated quaternized chitosan (QCS) and the nitric oxide (NO) donor N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine (BNN6). The B-QCS–BNN6 nanoplatform [
111] exhibited photothermal therapy efficacy and provided controlled NO release after 808 nm laser irradiation, reaching fast >99.9% inactivation of bacteria.
Table 1.
Representative new inorganic-based PTAs nanomaterials for antibacterial activity.
Table 1.
Representative new inorganic-based PTAs nanomaterials for antibacterial activity.
Type of nanomaterials |
Characterisation Morphology |
Tested bacteria |
PTT parameters |
Performance |
Ref. |
Metalic based PTAs |
Au NR |
10 × 45 nm Au NR attached to glass surfaces |
S. epidermidis ATCC 35984 |
LED - 850 nm, I=0.2 W·cm-2, 5 min |
AR=71% of biofilm Max- 97% |
[61] |
Au nanaworms covered with PDA |
Nanoworms with diameters of 5 ± 1.5 nm, interconnected |
E. coli S. aureus
|
808 nm I=1 W·cm-2, 20 min 100 µg·mL-1 PTAs |
∆T= 30.9 °C AR=80% E. coli and AR=90% S. aureus |
[67] |
glycomimetic polymers decorated Au NR |
AuNR- 50–100 nm long |
drug-resistant P. aeruginosa |
808 nm laser, I=2 W·cm-2, 5 min 125 μg·mL−1 PTAs |
∆T= 15.4 °C AR=80%
|
[71] |
Protease (bromelain) -conjugated AuNR |
Au NR -32 nm length, 7.8 nm width |
E. coli S. aureus
|
808 nm 50 μg·mL−1 PTAs |
Tmax = 66°C AR=96.8% E. coli AR=97.9% S. aureus
|
[72] |
Peptides/neuropeptide conjugated AuNR |
Au NR - 49 nm length and 11 nm width |
MRSA E. coli
|
808 nm I= 2 W·cm-2 , 4 min |
Tmax ~70 ◦C stable after 4 cycles AR= 99% for MRSA AR= 96% for E. coli
|
[73] |
AuAg yolk−shell cubic nanoframes |
well-defined cubic nanoframes 10 nm Au core and frame edge length: 25- 60 nm; frame thickness: 3.8 - 6.1 nm Ag/Au ≈ 3:1, |
MRSA E. faecalis P. aeruginosa K. pneumoniae B. bacillus E. coli
|
808 nm laser I=0.33 W·cm-2, 10 min |
η = 65.6% at 0.27 W·cm−2 ‘; ΔT = 23.7 °C AR=96.55%, P. aeruginosa AR=93.69% K. pneumoniae AR=92.34 % B. bacillus AR=96.73%, E. coli AR=98.08% E. faecalis |
[76] |
fractal-like Ag nanoaggregates in SiO2 deposited on PDMS layer |
AgNPs 10-20 nm, few nm interNPs distances SiO2 =1.3-25% |
S. aureus and E. coli
|
808 nm laser I=1.4 W·cm-2, 10 min; m=15.4 μg Ag/SiO2
|
η = 50% AR=100% of S. aureus biofilm (10 min) AR=100% of E. coli biofilm (5 min.) |
[74] |
Pd NPs |
4 nm and 41 nm in diameter |
S. aureus and E. coli. |
808 nm laser , I= 1.35 W·cm-2, 10 min, 20 mg·L−1 PTAs |
η = 33.1% AR=99.99% S. aureus AR=99.99% E.coli.
|
[81] |
Ag /Au bimetallic NPs on Jellyfish Nanofibers scaffold |
Bimetallic Ag/AuNPs: nanospheres, nanotriangles |
B. subtilis P. aeruginosa E. coli, S. epidermidis |
808 nm NIR laser, I= 1 W·cm-2, 5 min |
Tmax= 80 °C. Effective (AR=n.a.) |
[83] |
Pd-Cu nanoalloy NPs+ AMO in ZIF-8 |
Spherical Pd-Cu nanoalloy NPs size 9.02 nm |
S. aureus P. aeruginosa
|
λ = 808 nm NIR laser, I = 1 W·cm-2 , 10 min, 200 μg·mL−1 PTAs |
η = 45.8% AR=99.8% S. aureus AR=99.1% P.aeruginosa CR= 75.3% S. aureus CR= 74.8% P. aeruginosa
|
[84] |
Sulfides |
Cu7S4 nanosheets |
Cu7S4 samples with (224) exposed facet, a large number of nanosheets, diameter of 30–50 nm. |
B. subtilis, E. coli drug-resistant P. aeruginosa
|
808 nm laser, I= 1.5 W·cm-2, 10 min, 50 μg·mL−1 PTAs |
η = 40.52% ∆T= 29.4 °C AR= 100% E. coli AR= 100% B. Subtilis , AR> 90% P. aeruginosa |
[88] |
CuS@GDY |
graphdiyne nanowalls wrapped hollow CuS nanocubes |
MRSA and E.coli
|
808-nm laser, I=0.4 W·cm-2, 10 min |
η = 48%, ∆T= 28 °C AR >99.999% MRSA AR >99.999% E.coli
|
[79] |
CuS nanosheets with sulfur vacancies |
Nanosheets: Diameters= 60–100 nm the thickness =25–30 nm |
B. subtilis and E. coli
|
808 nm laser, I=1.2 W·cm-2, 10 min 50 μg·mL−1 PTAs |
η = 41.8%, ∆T= 30 °C, AR=99.999% (both) |
[85] |
sulfur vacancy modulated MoS2
|
Nano spheres- diameter 200–300 nm |
E. coli. |
808 nm laser, I=1.5 W·cm-2; 10 min 50 μg·mL−1 PTAs |
η = 45.97% ∆T 32 ◦C ≈100% killed bacteria |
[89] |
Cu doped MoS2 nanoflowers |
Nanospheres of 50-500 nm; Cu2+ were uniformly distributed on the surface edge sites |
S. aureus |
660 nm laser, I=0.898 W·cm-2, 20 min., 2 μg·mL−1 PTAs |
∆T= 30.3 °C AR=99.64% |
[90] |
NiS2 nanozymes |
Spherical NPs- diameter of 112 nm |
E. coli, DH5α MRSA,Mu50 |
808 nm laser, I=0.75 W·cm-2, 10min, 75 μg·mL−1 PTAs |
η = 43.8% ∆T= 23.4 °C AR=E.coli 98.33% AR≈92% MRSA |
[91] |
selenides |
SnSe |
spherical particles |
E. coli and B. subtilis
|
808 nm laser, I=1.5 W·cm-2, 10 min 25 μg·mL−1 PTAs |
η =41.4% Tmax =57 °C AR=99.99% E. coli and AR=99.99% B. subtilis
|
[93] |
Cu2Se NPs in PVDF membrane |
80 nm size NPs |
E. coli and
|
1064 nm laser, I= 2.0 W·cm-2, 400 s 160 μg·mL−1 PTAs |
η =30.8% ∆T= 14.6 °C AR=97.52% E. coli |
[92] |
Oxides |
Fe3O4 NPs |
mesoporous hollow Fe3O4 NPs |
E. coli S. aureus
|
808-nm NIR + H2O2 (1mM) I=1 W·cm-2 ,10 min; 4 cycles 1 mg·mL−1 PTAs |
η =28.5% AR=72% S. aureus and AR=100% E. coli |
[94] |
magneto-plasmonic Fe3O4@Au core@shell |
spherical core of Fe 3O4 and Au - branched structure |
E. coli S. aureus
|
980 nm laser diode, I=1.0 W·cm-2, 10 min, 50 μg·mL−1 PTAs |
η = 69.9% AR=100% E. coli and AR=100% S. aureus
|
[95] |
MXene |
Ti3C2 MXene combined with Cip |
Ti3C2 nanosheets monolayer with 50–200 nm lateral size |
E. coli MRSA
|
808 nm, I=0.4 W·cm-2 , 15 min, 100 μg/mL Ti3C2+ 5 mg/mL Cip |
Tmax =60.7 °C AR= > 99.99999% |
[99] |
Ti3C2TX MXene-PDA functionalized +lysozyme |
Ti3C2 MXene - monolayer |
MRSA |
808 nm laser, I=2.0 W·cm-2, 15 min. 50 μg·mL−1 PTAs |
η = 46.88% Tmax =63.5 °C. AR>95 % MRSA |
[98] |
Bi2S3NR/Ti3C2Tx MXene |
Ti3C2Tx Mxene few-layer nanosheets |
E. coli S. aureus
|
808 nm light, I= 0.7 W·cm-2 , 10 min |
η = 35.43% Tmax =65 °C RA=99.86% S. aureus RA=99.92% E. coli |
[100] |
Other |
BPs@cationicCDs |
few-layer or monolayer BPs with a flat structure CDs (8–13 nm) grew in situ by BPs |
E. coli S. aureus
|
660 nm + 808 nm laser, I=1.5 W·cm-2, 5 min , 200 μg·mL−1 PTAs |
η = 34.1% ∆T= 28.2 °C RA≈99 % S. aureus and E. coli |
[106] |
BPQDs@NH |
BP quantum dots (BPQDs) of 3 nm encapsulated in hydrogel |
MRSA Amp r E. coli
|
808 nm laser, I = 1 W·cm-2, 5 min, 200 μg·mL−1 PTAs |
η = 42.9% ∆T= 35 °C RA= 90% MRSA RA= 90% Ampr E. coli
|
[112] |
Carbon-based nanomaterials
Carbon-based nanomaterials have attracted considerable attention as photothermal agents (PTAs) for antimicrobial applications, owing to their distinctive structure and outstanding optical, thermal/electronic, and mechanical properties, versatility in functionalisation, and high surface area [
113], deep tissue penetration, and reduces mammalian cytotoxicity.[
114]
Currently, from the entire carbon-based nanomaterials library, graphene-based nanomaterials (GBNs) and carbon nanotubes (CNTs) have become the hot spots to eradicate and deactivate bacteria
via various physical and chemical antibacterial mechanisms such as chemical oxidation and ROS generation, biological isolation of microbial cells, generation of structural damages,[
49] as well as photothermal effects [
115,
116], mainly being investigated as antimicrobial PTAs. The antibacterial properties of GBNs appear to be influenced by the presence and number of functionalities from their surface.[
116] At the same time, CNTs are characterized by a size-dependent antibacterial activity that increases with a decrease in size.[
117] Green fluorescent commercial graphene quantum dots (GQD) were tested as a photoactive antimicrobial agent, and a heat yield of 50% (measured by the photothermal lens technique) was obtained under excitation at 532 nm (wavelength shorter than the emission band), proving the potential to be an efficient, safe, and low-cost photothermal agent.[
118] Carbon dots have also been tested due to their biocompatibility and versatility. One study reports the utilisation of bacteria-affinitive carbon dots targeting the D-Glutamic acid-adding enzyme (MurD ligase), which is involved in bacterial cell wall peptidoglycan synthesis.[
119] Bacterial testing showed the ability of this material to kill 80.33% of
E. coli and 89.27% of
S. aureus without NIR light and, only after a few minutes of laser irradiation, more than 96% of
E. coli and 100%
S. aureus were killed, proving an increased spatial accuracy of the antibacterial action with minimal cytotoxicity to human cell lines.
In fact, as PTAs for antimicrobial applications, the carbon-based nanomaterials are usually combined with various compounds to improve the antibacterial performances through synergistic or additive effects, since their intrinsic photothermal properties, in some cases, cannot be sufficient to assure an appropriate antibacterial effect in a particular application. Thus, a great variety of reasonable
carbon-based combinations with photothermal components (e.g., Au nanostars [
120], fluorophores [
121]) and antibacterial compounds (i.e. Ag NPs [
122,
123] have been designed and reported in the literature as efficient PTAs with adequate antibacterial activity in various practical applications (
Table 2). For instance, Oruc
et al. [
121] decorated the surface of multiwalled carbon nanotubes (MWNT) with NIR-absorbing 3,3′-diethylthiatricarbocyanine (DTTC) fluorophores to obtain efficient photothermal nanomaterials that can kill
Pseudomonas aeruginosa. Under NIR irradiation, the formulated MWNT/DTTC nanohybrids could produce a poweful hyperthermal effect (the temperature of the dispersion reached around 92°C after 15 min), leading to a 77% killing efficiency of
P. aeruginosa cells. Then, the MWNT/DTTC nanohybrids were embedded within a waterborne polyurethane matrix. It was noted that under laser irradiation, the temperature increased to 120 °C, generating a substantial antibacterial and antibiofilm effect on
P. aeruginosa cells attached to the surface. Further, Tan
et al. [
122] combined the excellent photothermal effect of RGO and intrinsic antibacterial features of AgNPs into RGO/Ag nanocomposite to destroy both common bacteria (
E. coli) and multidrug-resistant (MDR) bacteria (
Klebsiella pneumoniae). Among the investigated samples, RGO/Ag nanocomposite presented a significantly higher antibacterial activity against both bacteria, which synergistically increased under NIR irradiation (0.30 W/cm
2 for 10 min) through the photothermal effect that induced the cell membrane disruption and generation of ROS. In another work, Yang
et al. [
124] explored the synergy of photocatalytic-photothermal effects embedded in a stable BiOI-GO nanocomposite with better environmental disinfection properties, while Lv
et al. [
125] combined polyvinylpyrrolidone-functionalized AgNPs with rGO (AgNPs-PVP@rGO) into a visible-light-triggered photoactive nanocomposite able to increase the visible-light-driven photocatalytic degradation and photothermal antibacterial activity.
Albeit carbon-based nanomaterials are characterized by a series of advantages, such as profuse source, low cost, thermal and mechanical stability, good processability, and high thermal conductivity, besides biocompatibility issues, the relatively low photothermal effect for antibacterial activity represents the main drawback as PTAs, particularly when compared to photothermal effect generated by the inorganic or noble metals-based nanomaterials.
3.2. Organic based PTAs
Recently, organic compounds-based nanomaterials have received increasing attention as potential alternatives to inorganic-based nanomaterials, being extensively exploited in formulating PTAs with proper antibacterial activity. As PTAs, these compounds typically absorb photons produced by NIR irradiation and generate heat through non-radiative relaxation pathways. The category of organic-based PATs nanomaterials is generally represented by conjugated polymers-based nanomaterials (i.e., polyaniline, polypyrrole), crystalline porous organic polymers (e.g., covalent organic framework) and polymer functionalised nanomaterials.
Conjugated polymer (CP)-based nanomaterials
Among various classes of macromolecules, conjugated polymers (CP) with absorption in the NIR range, such as polydopamine (PDA), polyaniline (PANI), polypyrrole (PPy), or poly(3,4-ethylenedioxythiophene) (PEDOT), are widely explored in designing new light-responsive nanomaterials with suitable antimicrobial and bactericidal performances. Besides the inherent electronic and optical features originating from the specific delocalised electronic structure and the presence of large π-conjugated backbones [
117,
126], CP is characterized by low light scattering and high penetration depth of NIR light in tissue, amenability in formulation, as well as higher biocompatibility than carbon-based nanomaterials, capable of mitigating their main drawback related to agglomeration.[
126] To maximize the bacterial interaction capability, aqueous stability, and antimicrobial PT effect, CP is usually modified with different compounds (i.e. cationic ammonium groups, PEI, Au nanorods, Au NPs, magnetic NPs) (
Table 2).[
127] Zhou
et al. [
128] formulated positively charged conjugated polymer (PTDBD)-based NPs with NIR-triggered activity and better bacterial interaction ability for antimicrobial therapy to advance the phototherapy for bacterial infections,. Under a low power light density of 1 W·cm
−2 (808 nm) and a short time of 8 min, simultaneous ROS and heat generated by the polymer PTDBD with donor-acceptor (D–A) structure could effectively kill three representative microbes (e.g.,
Ampr E. coli,
S. aureus, and
C. albicans. Further, the authors investigated the efficacy of this strategy
in vivo for treating
S. aureus-infected wounds of mice, noticing no significant damage to normal tissue, demonstrating its great potential in the application of treatment for bacterial infections. Later, Zhang
et al. [
84] used the same strategy to design cationic conjugated PDTPBT NPs for photothermal antibacterial therapy under NIR light irradiation. Based on the
in vitro experiments, the constructed PDTPBT exhibited efficacious antibacterial ability upon 808 nm laser irradiation, besides excellent photostability and high photothermal conversion efficiency. In another work, Ko
et al. [
129] constructed a photothermal nanocomposite based on poly(3,4-ethylenedioxythiophene): poly(styrene-sulfonate) (PEDOT: PSS) and agarose with thermo-processability, light-triggered self-healing, and excellent antibacterial activity. The authors demonstrated that during NIR exposure, PEDOT: PSS/agarose exhibited high shape flexibility through the NIR light-induced self-healing effect after damage and excellent antibacterial activity against pathogenic bacteria, successfully destroying and killing
E. coli and
S. aureus within 2 min of irradiation.
Polymer functionalised nanomaterials
Functionalising nanomaterials with specific polymers (i.e. PEG, chitosan, peptides) is a widely exploited strategy that, besides improving biocompatibility, dispersibility, protection in the biological environment and specific targeting, may increase the physicochemical properties or endow the newly formulated nanomaterials with specific functions, advancing their effectiveness in PATs in practical antibacterial applications [
130] (
Table 2). In this respect, Fan
et al. [
131] managed to construct photothermal NPs that could efficiently kill
E. coli at a relatively low temperature of ~45 °C under NIR irradiation by linking PDA NPs with thiolated poly-(ethylene glycol) (PEG) and magainin I (MagI) for increasing the stability and bacterial interaction specificity. Jia
et al. [
132] constructed a versatile graphene-based photothermal nanocomposite that could rapidly and effectively eliminate Gram-positive -
S. aureus and Gram-negative -
E. coli bacteria, supplementary destroying bacterial biofilms upon NIR irradiation. In this sense, the authors combined the efficient ability of chitosan to capture the bacteria by its positively charged functional groups with magnetic NPs and the photothermal conversion efficacy of GO. The formulated multifunctional nanocomposites could eliminate bacteria effectively after 10 min of NIR irradiation and destroy bacterial biofilms, suggesting their great potential in antibacterial applications. In another work aiming at resolving focal infection generated by antibiotic-resistant bacteria, Korupalli
et al. [
133] used the same strategy. They developed pH-responsive self-assembly into NPs based on polyaniline-conjugated glycol chitosan (PANI-GCS). The authors estimated that under NIR irradiation, the local temperature of PANI-GCS NPs increased by approximately 5°C leading to the specific and direct aggregation of bacteria, avoiding tissue damage, and promoting the wound healing. Furthermore, Wang
et al. [
134] proved that the functionalisation of photothermal-responsive conjugated polymer nanoparticles with cell-penetrating peptide (CPNs-Tat) might be considered a rapid and effective modality for combating bacterial infections. The positively charged Tat from the surface of NPs could efficiently enhance the interaction with bacteria cells leading to CPNs-Tat/bacteria aggregation. At the same time, under NIR irradiation, CPNs-Tat could convert the light into heat efficiently and produce local hyperthermia to kill bacteria within a few minutes.
Covalent organic frameworks
Covalent organic frameworks (COFs) represent crystalline organic frameworks of porous polymers. Besides, good thermal stability, reduced toxicity, and versatility in functionalisation contain specific light atoms (carbon, nitrogen, oxygen, and borane), tailored and harmonious porosity.[
135,
136] These features enable them to be considered tremendous candidates for developing suitable platforms for application in different fields (i.e. gene and drug delivery, bioimaging, biosensing) [
135], mainly being used as wound healing and antibacterial agents, owing to their long-lasting antibacterial properties and ability to interact with the bacterial cells through their hydrophobic spatial structures.[
137] In addition, the encompassed light lightweight elements, strongly connected with covalent bonds along with specific 2D (two-dimensional) or 3D (three-dimensional) π-conjugation structure, make them critical light-activated agents for photothermal and photodynamic antibacterial effect, as well as in combinatorial therapies [
135,
136,
137,
138]. Porphyrin-based COF (TP-Por-CON) containing nitric oxide (NO) donor molecule, BNN6, within the pore volume of the framework structure for synergizing photodynamic, photothermal and gaseous therapies under red light irradiation (635 nm) and efficiently killing Gram-negative bacteria
E. coli and Gram-positive bacteria
S. aureus in vitro was successfully synthesized.[
139] Yang
et al. [
140] reported the construction of a covalent organic framework (TAPP-BDP) with a conjugated donor-acceptor) structure. Under the NIR-irradiation (λ = 808 nm), it can exercise triple and synergistic bacterial inhibition by combining photodynamic, photothermal, and peroxidase-like enzymatic activities. Based on
in vitro investigations, the authors proved the excellent antibacterial efficiency of TAPP-BDP against Gram-negative and Gram-positive bacteria. At the same time, the
in vivo experiments further suggested the ability of materials to heal wounds infected with
S. aureus in animals. Recently, Li
et al. [
136] have proposed a rational strategy for treating drug-resistant pathogenic bacterial infection by constructing a hydrogel with photocatalytic and anti-inflammatory activities based on Cu co-coordinated D- A type COF and sodium alginate hydrogel (CTCS) for adequate healing of wound infection. Under the NIR-irradiation (λ = 660 nm), the CTCS hydrogel presented an excellent bactericidal activity originated from the synergy of photothermal and photocatalytic effects, killing 99.95% and 98.5% of
S. aureus and
E. coli of bacterial strains within the first 20 min.
In vivo experiments confirmed that CTCS hydrogel could be used as a strategy for rapid reconstruction of bacterially infected tissues, owing to their ability to reduce the expression of TNF-α and promote wound healing and tissue regeneration (IL-10 and VEGF).
Table 2.
Representative C-based and organic-based PTAs nanomaterials for antibacterial activity.
Table 2.
Representative C-based and organic-based PTAs nanomaterials for antibacterial activity.
|
Matrix/ material
|
Light (nm) and power |
Temperature reached |
Antibacterial mechanism |
In vitro biological performances |
Ref |
Type of bacteria |
Efficacity |
|
Carbon-based nanomaterials |
rGO/AuNP |
808 nm; 3.0 W/cm2
|
73.5 °C |
PTT |
S. aureus E. coli
|
100% |
[120] |
MWNT/DTTC |
808 nm; 1.0 W/cm2
|
92 °C, 120 °C |
PTT |
P. aeruginosa |
77% -100% |
[121] |
GO/Ag |
808 nm; 1.5 W/cm2
|
24.6 °C |
PTT & Ag+ release |
MDR E. coli |
̴ 96% |
[123] |
rGO/Ag |
808 nm; 0.30 W/cm2
|
Higher with ̴ 20 °C |
PTT &Ag+ release |
E. coli, K. pneumonia
|
100% |
[122] |
AgNPs PVP@rGO |
Visible-light |
- |
PTT & Ag+ release & physical wall demolition |
E. coli |
Effective |
[125] |
Fe3O4@GO-QCS |
808 nm; 3.0 W/cm2
|
≥50 °C |
Bacteria capture & PTT & Magnetic Recycle |
S. aureus E. coli
|
̴ 100% |
[141] |
Fe3O4-CNT-PNIPAM |
808 nm; 3.0 W/cm2
|
- |
Bacteria capture & PTT & Magnetic Recycle |
S. aureus E. coli
|
̴ 100% |
[142] |
CP |
PTDBD |
808 nm; 1.0 W/cm2
|
66 °C |
PTT |
S. aureus E. coli C. albicans
|
Effective |
[128] |
PDTPBT |
808 nm; 1.0 W/cm2
|
57 °C |
PTT |
E. coli MRSA
|
Effective |
[84] |
PEDOT:PSS/agarose |
808 nm; 2.0 W/cm2
|
24.5 °C |
PTT |
S. aureus E. coli
|
̴ 100% |
[129] |
PDPP3T |
808 nm; 0.50 W/cm2
|
̴ 45°C |
PTT |
E. coli |
̴ 100% |
[143] |
DMCPNs |
808 nm; 0.50 W/cm2
|
62.4 °C |
PTT & PDT |
E. coli |
93% |
[144] |
Polymer functionalized nanomaterials |
MagI-PEG@PDA NPs |
808 nm; 2.0 W/cm2
|
45 °C |
PTT |
E. coli |
99.99% |
[131] |
GO–IO–CS nanocomposite |
808 nm; 2.0 W/cm2
|
̴ 25°C |
PTT & capture bacteria & aggregation |
S. aureus E. coli
|
̴ 80% |
[132] |
CPNs-Tat |
808 nm; 2.0 W/cm2
|
55.3 ºC |
PTT |
E. coli S. aureus C. albicans
|
̴ 100% |
[134] |
SF-CS-PDA cryogels |
808 nm; 2.0 W/cm2
|
̴ 45 °C |
PTT & ROS-scavenging capacity, tissue affinity |
S. aureus E. coli
|
Effective |
[145] |
COFs |
TP-Por-CON@BNN6 |
635 nm |
- |
PTT & PDT & gaseous therapy |
S. aureus E. coli
|
Effective |
[139] |
TAPP-BDP |
808 nm |
65 °C |
PTT & PDT & ROS |
S. aureus E. coli
|
Effective |
[140] |
CTCS |
660 nm 0.4 W/cm2
|
̴ 54 °C |
PTT & PDT |
S. aureus E. coli
|
> 98.5% |
[136] |
Although the photothermal effect of organic-based nanomaterials usually does not outperform that of inorganic materials, these materials have attracted tremendous attention as PTAs, owing to biocompatibility and potential biodegradability, essential features that are missing in the case of inorganic materials, and which can be further fine-tuned depending on the targeted application.
Among investigated materials, CP and COFs are characterized by relatively good biocompatibility, significant absorption coefficient, and high photothermal conversion efficiency. In contrast, besides the acceptable biocompatibility, functionalised polymer nanomaterials, are endowed with specific targeting segments, which may resolve the most faced challenge of nanomaterials and the agglomeration process and increase the PTT performances as antibacterial.
Despite many optimistic outcomes of organic-based PTT, there are still practical barriers to clinical translation. First, their synthesis/formulation can be expensive and laborious, so simple preparation methods for scale-up are still needed. Second, in vitro and in vivo studies related to long-term biosafety are still in their infancy and are challenging. At the same time, the biodegradation mechanism of complex organic structures such as PTAs in living organisms still needs to be investigated. Therefore, further investigation is required to design more biocompatible organic-based PATs with predictable biodegradation mechanisms and biological behaviour that would satisfy PTT efficacy.
3.3. Hybrid photothermal antimicrobials and inorganic-organic nanocomposites
Metal-organic framework (MOF)-derived hybrid materials developed as promising multifunctional nanomaterials or nanocarriers for medical applications such as diagnosis and antimicrobial therapy. [
146] Moreover, NPs can be incorporated into the hydrogels and used as nanocomposite hydrogels. The NPs can be added directly to the hydrogels, produced in situ via reaction within the hydrogels, or mixed with a hydrogel precursor to undergo gelation and form the final NPs hydrogel. Interestingly, the nanocomposites’ high chemical or physical complexity allows synergistic effects and better functionality.[
147] Therefore, hybrid nanosystems have been increasingly developed for their versatility and efficacy in overcoming obstacles not readily surmounted by nonhybridised counterparts.
For instance, rough surface nanoparticles with satisfactory biocompatibility, such as carbon-iron oxide nanohybrids with rough surfaces (RCF) [
148] or NiFe
2O
4@Au/PDA[
149] demonstrated antibacterial effects via synergistic photothermal therapy (PTT)/chemodynamic therapy (CDT) effects in the NIR-II bio-window and photothermal-magnetolytic, respectively. The nanostructures presented increased bacterial adhesion for effective interaction, better penetration depth and low power density in vitro and
in vivo studies against E. Coli, S. Aureus, and MRSA. Excellent antibacterial activity against S. aureus (99.7%) and P. aeruginosa (99.9%) occurred under heat-induced antimicrobial agent physcion(Phy)release from the drug-loaded black phosphorus nanosheets (BPNSs@phy).[
150] The BPNSs presented excellent photothermal conversion ability, which disturbed the hydrophobic interactions that kept the antibiotic onto the nanosheets and facilitated Phy release, thus the PTT/CDT synergism for a better bactericidal effect.
Furthermore, loading hydrogels with nanoparticles increased their functionality. The fluorescent carbon dots (CDs) employed as carriers for curcumin (Cur) within the CDs/Cur Nanocomposite [
151] exhibited low cytotoxicity and negligible haemolytic activity. IK8-liposome/AuNR-loaded hydrogels [
152] incorporated antimicrobial peptides-loaded liposomes, IRIKIRIK-CONH
2(IK8) and gold nanorods (AuNRs) into poly(ethylene glycol) (PEG) to protect them from proteolysis and to employ the PTT capacity for a controllable PTT/CDT synergistically enhanced antibacterial nanoplatform against S. aureus and Pseudomonas aeruginosa.
Enhancing the antibacterial activity of silver ions (Ag+) was possible through a silver nanoparticle-embedded carrageenan hydrogel, the gallic acid-modified silver nanoparticles (GA-Ag NPs Carr)[
90] and antimicrobial peptides-gold/silver nanorods (Dap@Au/Ag NRs)[
153] capable of destroying the integrity of the MRSA membrane and resulting in content leakage and bacterial death. The platforms expressed PTT/CDT enhanced antibacterial activity via Ag+ released from the NPs and NRs, and NIR laser-induced photothermal assistance GA-Ag NPs and Au/Ag NRs. The hydrogels also presented good biocompatibility and effective anti-
S. aureus,
MRSA and
E. Coli activity and healing-promoting properties
in vivo. Similarly, wound healing was accelerated in diabetic rats when studying a black phosphorus quantum dots-based hydrogel (BPQDs@NH).[
154] The MRSA-infected wounds exposed to the combined PDT/PTT were effectively sterilised due to the rapid increase in temperature (up to 55 °C), ROS production, lipid peroxidation, glutathione, adenosine triphosphate accumulation and bacterial membrane destruction. 99.64% efficacy against
Staphylococcus aureus resulted from the enhanced photocatalytic and photothermal performances of Molybdenum disulfide (MoS
2) nanosheets doped with copper ions (MoS
2@Cu
2+).[
90] The underlying MOA consists of the combined hyperthermia, ROS and Cu
2+ release. The Cu
2+, by absorbing photons and converting the photoenergy into heat (the d–d transition of electrons), contribute to intense PTT. At the same time, the Cu
2+ also absorbs the photogenerated electrons from MoS
2 and contributes to enhanced ROS (reducing electron-hole recombination). Despite the promising initial results, developing effective MoS
2-based antibacterial nanomaterials is still problematic due to the hydrophobicity and the weak interaction with bacteria and ROS. Therefore, constructing polyethylenimine modified Molybdenum disulfide (MoS2-PEI) nanocomposite enhanced the stability and promoted the binding to the surface of bacteria through electrostatic interactions for enhanced photothermal antibacterial activity [
155] and even a combined chemo/photothermal/photodynamic triple-mode therapy of bacterial and biofilm infections. [
156] Under NIR light irradiation, MoS
2-PEI exhibited evident synergistic antibacterial efficacy against
Escherichia coli and
Staphylococcus aureus with a long-term bactericidal effect. High-efficiency bactericidal and long-term bacteriostatic effects with less bacterial rebound were observed in an MRSA-induced murine abscess under PTT with Ti3C2MXene-based hybrid hydrogel. The rationally designed MXene-based hybrid hydrogels provided a strategy for cost-effectively treating localized bacterial infection by nanosystems.[
99] Exploiting the photothermal sensitivity and peroxidase-like activity against one strain of vancomycin-intermediate S. aureus reference strain and E. coli proved successful due to the encapsulated tungsten sulfide quantum dots (WS
2QDs) and vancomycin (VAN) in thermal-sensitive liposomes. Interestingly, the enzymatic properties of WS
2QDs, the intrinsic and the temperature-dependent ones, contributed to the improved CDT efficacy, illustrating the platform’s potential as one controllable system. The nanosystem also achieved antibiofilm properties via biofilms’ disruption for better drugs’ transmembrane passage. Moreover, the in vivo studies highlighted biocompatibility and the possibility of engaging the synergistic chemodynamic/photothermal antibacterial effects as reliable therapeutic approaches.[
157] One complex nano-platform based on a hybrid structure was proposed as a novel therapeutic option for MRSA skin infections. In this case, the system incorporated two-layered microneedle (MN) arrays: one water-insoluble inner layer with NIR photothermal capacity was encased by one water-soluble external layer loaded with vancomycin (VAN). The photothermal core comprised flame-made plasmonic Au/SiO
2 nanoaggregates and polymethylmethacrylate (PMMA). The evaluation showed a synergistic CDT/PTT (VAN and heat above 55 °C for 10 min) effect, which reduced the methicillin-resistant
Staphylococcus aureus (MRSA) survival by up to 80%.[
158] The antibacterial and wound-healing capacity of injectable and self-healing hybrid hydrogels showed high-efficiency photothermal antisepsis under mild PTT conditions. The hybrid hydrogel prepared by self-polymerising dopamine into polydopamine and synchronised reduction of Ag
+ to Ag NPs within a chitosan scaffold presented spontaneous recovery after mechanical damages, maintained the structural integrity, and recovered the original admirable antimicrobial functions
in vitro and
in vivo with no obvious toxicity.[
159] Since the toxicity of certain nanocomposites such as AuNPs needs to be mitigated prior to incorporating them into nanoplatforms for biological use, one strategy was proposed: having the AuNPs immobilized onto a larger particulate system, a natural clay halloysite nanotubes (HNTs) and the HNTs modified with antibodies against
Escherichia coli (
E. coli, as a model microorganism) for immune-targeted PTT. The resulting AuNR-Ab-HNTs hybrids demonstrated that the harnessing antibody-functionalized HNTs as carriers increase the potential of the functionalised PTT/immunotherapy nanoplatforms for targeted delivery of antibacterial nanoparticles combinations (e.g., silver or metal oxides) or antibiotics for the localized antimicrobial infections.[
160]
In conclusion, the advances in nano-biotechnology are promising and pave the way towards NIR-controlled multimodal potent antibacterial hybrid platforms without apparent toxicity. Designing and manufacturing intelligent nanosystems as more effective and selective alternatives will address the worldwide expansion of antibiotic-resistant species and the need to protect the microflora from non-specific antibiotics.