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Biofilm Impeding AgNPs Target Skin Carcinoma by Inducing Mitochondrial Membrane Depolarization Mediated through ROS
Debasis Nayak1, Manisha Kumari1, Sripathi Rajachandar1
1Immunology and Molecular Medicine Laboratory, Department of Life Science, National Institute of Technology , Rourkela, Odisha 769008, India.
Abstract:
Reactive oxygen species (ROS) are a double-edged sword that possesses both beneficial and harmful effects. Although basic research on skin cancer prevention has undergone a huge transformation, cases of recurrence with higher rates of drug resistance are some of its drawbacks. Therefore, targeting mitochondria by ROS overproduction provides an alternate approach for anticancer therapy. In the present study, green-synthesized silver nanoparticles (AgNPs) were explored for triggering the ROS production in A431 skin carcinoma cells. The synthesized AgNPs were characterized for size, charge, morphology, and phase through high-throughput DLS, Fe-SEM, XRD, and ATR-FTIR techniques. Their physiochemical properties with hemoglobin and blood plasma were screened through hemolysis, hemagglutination assay, and circular dichroism spectroscopy confirmed their nontoxic nature. The AgNPs also exhibited additional efficacy in inhibiting biofilm produced by V. cholerae and B. subtilis, thereby facilitating better applicability in wound-healing biomaterials. The depolarization of mitochondrial membrane potential ΔΨm through excess ROS production was deduced to be the triggering force behind the apoptotic cell death mechanism of the skin carcinoma. Subsequent experimentation through DNA fragmentation, comet tail formation, cell membrane blebbing, and reduced invasiveness potentials through scratch assay confirmed the physiological hallmarks of apoptosis. Thus, depolarizing mitochondrial membrane potential through green-synthesized AgNPs provides an economic, nontoxic, specific approach for targeting skin carcinoma with additional benefits of antibacterial activities.
Insights
Green-synthesized silver nanoparticles (AgNPs) induce reactive oxygen species (ROS) to trigger apoptosis in skin carcinoma cells. This novel approach offers a non-toxic, targeted therapy with added antibacterial benefits for wound healing.
Area of Science:
- Nanomedicine
- Biochemistry
- Dermatology
Background:
- Reactive oxygen species (ROS) have dual roles, but their overproduction can be leveraged for cancer therapy.
- Skin cancer recurrence and drug resistance necessitate novel therapeutic strategies.
- Mitochondrial targeting via ROS overproduction presents a promising avenue for anticancer treatment.
Purpose of the Study:
- To investigate green-synthesized silver nanoparticles (AgNPs) for their potential to induce ROS production and apoptosis in A431 skin carcinoma cells.
- To characterize the synthesized AgNPs and assess their biocompatibility and antibacterial properties.
- To elucidate the mechanism of AgNP-induced cell death, focusing on mitochondrial pathways.
Main Methods:
- Green synthesis of silver nanoparticles (AgNPs).
- Characterization of AgNPs using DLS, Fe-SEM, XRD, and ATR-FTIR.
- Assessment of AgNP biocompatibility via hemolysis, hemagglutination, and circular dichroism spectroscopy.
- Evaluation of antibacterial activity against V. cholerae and B. subtilis.
- Analysis of mitochondrial membrane potential, DNA fragmentation, comet tail formation, cell membrane blebbing, and scratch assay to confirm apoptosis.
Main Results:
- Green-synthesized AgNPs were characterized for their physicochemical properties.
- AgNPs demonstrated a non-toxic nature towards blood components and exhibited significant antibacterial activity against V. cholerae and B. subtilis.
- AgNPs successfully induced ROS production in A431 skin carcinoma cells, leading to the depolarization of mitochondrial membrane potential (ΔΨm).
- Apoptotic cell death was confirmed through DNA fragmentation, comet tail formation, cell membrane blebbing, and reduced invasiveness.
Conclusions:
- Green-synthesized AgNPs are a safe and effective agent for inducing apoptosis in skin carcinoma cells by targeting mitochondrial pathways.
- AgNPs offer a dual therapeutic benefit, acting as an anticancer agent and possessing antibacterial properties beneficial for wound healing applications.
- This approach provides an economic, non-toxic, and specific strategy for skin carcinoma treatment.
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