A new approach to apoptotic gene expression control using nanoparticle-enhanced wound dressings for antibacterial and anticancer applications

: Skin cancer poses a major global health issue, with increasing incidence and mortality. Despite surgical advancements, recurrence, and complications persist. Bacterial infections during wound healing delay recovery, raise healthcare costs and may jeopardize treatment success. Nanotechnology presents a viable solution to these issues. This study explores a new anti-cancer wound dressing film infused with antibacterial nanoparticles containing dacarbazine. By merging dacarbazine’s anticancer effects with the nanoparticles' antibacterial properties, this dressing seeks to tackle skin cancer recurrence and wound care effectively. Our innovative bandage will slowly deliver dacarbazine at the surgical site while preventing bacterial infiltration, aiming to enhance treatment effectiveness, lower complication risks, and improve patient outcomes. Methods: ۱- Nanoparticles synthesis: ZIF-۸/ZnAl-LDH was synthesized via a two-step process. Pre-synthesized ZIF-۸ was dissolved in a NaOH solution, then combined with a solution containing Zn(NO۳)۲·۶H۲O and Al(NO۳)۳·۹H۲O. The mixture was heated to ۹۵ °C, adjusted to pH ۱۰, and stirred for ۲۴ hours. The resulting product was centrifuged, washed, and dried. ۲- In vitro tests: ۲-۱- Release profile: The film was immersed in ۱۰ mL PBS, pH ۷.۴, and shaken at ۳۷ °C. At set intervals, ۳ mL of the medium was taken out and replaced with fresh PBS. Released ZnAl-LDH/ZIF-۸-MOF was quantified using a UV–visible spectrophotometer ۲-۲- Bactericidal test: The antibacterial activities of the film were tested against pathogens S. aureus and P. aeruginosa. ۲-۳- Cell viability: The cytotoxic effects of drug-encapsulated film on A۳۷۴ cells were evaluated by MTT assay. ۲-۴- Gene Expression analysis: The in vitro effectiveness of drug-loaded film to alter the expression of apoptotic genes (bax, bcl-۲, and bad) was analyzed using real-time PCR. Results: Release profile: The in vitro release profile of ZnAl-LDH/ZIF-۸-MOF from the film mats, demonstrates a sustained release pattern. Bacterial test: Antibacterial assays of nanoparticle-loaded films against mentioned bacteria revealed that the biopolymers utilized in film preparation create an antibacterial zone around wounds. Cell viability: In the absence of drug loading, negative control, and blank film exhibited no cytotoxic effects on HFF۲ skin cells for up to ۷۲ hours. The drug-loaded film demonstrated an inhibitory effect on skin cancer cell proliferation after ۷۲ hours, confirming its retained biological activity. Gene expression: Firstly, the expression levels of all genes were normalized with the expression level of the housekeeping gene β-actin. Results showed that the mRNA expression levels of bax and bad genes were significantly up-regulated by the drug-loaded film relative to control cells. Also, it has been revealed that the mRNA levels of anti-apoptotic gene, bcl-۲, significantly down-regulated in the cells treated with nanoparticle-loaded films Conclusion: The developed nanoparticle-loaded wound dressing film effectively addresses skin cancer recurrence by regulating studied genes and tackling bacterial infections. The sustained release of dacarbazine, combined with the antibacterial properties of the nanoparticles, demonstrates promising potential for enhancing post-surgery wound healing and reducing complications. The film's biocompatibility and in vitro efficacy in inhibiting skin cancer cell proliferation and modulating apoptotic genes suggest its potential for clinical translation.

کلیدواژه ها:

anti-bacterial ، anti-cancer ، wound dressing ، apoptotic genes ، nanoparticle