PreprintArticleVersion 1This version is not peer-reviewed
Strongly ROS-Correlated, Time-Dependent and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation
Version 1
: Received: 6 September 2024 / Approved: 7 September 2024 / Online: 9 September 2024 (09:03:54 CEST)
How to cite:
Alfei, S.; Zuccari, G.; Athanassopoulos, C. M.; Domenicotti, C.; Marengo, B. Strongly ROS-Correlated, Time-Dependent and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation. Preprints2024, 2024090607. https://doi.org/10.20944/preprints202409.0607.v1
Alfei, S.; Zuccari, G.; Athanassopoulos, C. M.; Domenicotti, C.; Marengo, B. Strongly ROS-Correlated, Time-Dependent and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation. Preprints 2024, 2024090607. https://doi.org/10.20944/preprints202409.0607.v1
Alfei, S.; Zuccari, G.; Athanassopoulos, C. M.; Domenicotti, C.; Marengo, B. Strongly ROS-Correlated, Time-Dependent and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation. Preprints2024, 2024090607. https://doi.org/10.20944/preprints202409.0607.v1
APA Style
Alfei, S., Zuccari, G., Athanassopoulos, C. M., Domenicotti, C., & Marengo, B. (2024). Strongly ROS-Correlated, Time-Dependent and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation. Preprints. https://doi.org/10.20944/preprints202409.0607.v1
Chicago/Turabian Style
Alfei, S., Cinzia Domenicotti and Barbara Marengo. 2024 "Strongly ROS-Correlated, Time-Dependent and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation" Preprints. https://doi.org/10.20944/preprints202409.0607.v1
Abstract
Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drugs-induced secondary tumorigenesis and the emergency of drug resistance worsen the already worrying scenario, thus rendering urgent the development of new treatments, not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to act as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola-amphiphiles are capable to self-form nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, only recently the per se selective potent antibacterial effects of a TPP bola-amphiphile has been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties, on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola-amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC50 = 49 nM on MeOV after 72 h treatment). Upon these findings and considered the low cytotoxicity of BPPB against different mammalian not tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. In this sight, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents, but simply dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized with promising outcomes, such as high swelling capability, high porosity and viscous elastic rheological behavior.
Chemistry and Materials Science, Organic Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
