Conclusion
This work demonstrates the therapeutic application of silver nitroprusside as a multiple ROS generator utilizing Fenton like reaction. Thereby, our study exhibits a potential application of CDT against HGSOC (High Grade Serous Ovarian Cancer), a deadly cancer through altering the redox homeostasis.
Methods
A simple solution mixing procedure was used to synthesize AgNP as CDT agent. AgNP were structurally and morphologically characterized, and it was observed that a minimal dose of AgNP is required to destroy cancer cells with limited effects on normal cells. Moreover, comprehensive in vitro studies were conducted to evaluate antitumoral mechanism.
Results
AgNP have an effective ability to decompose endogenous H2O2 in cells. The decomposed endogenous H2O2 generates several different types of reactive species (•OH, O2•-) including peroxynitrite (ONOO-) species as apoptotic inducers that kill cancer cells, specifically. Cellular internalization data demonstrated that in short time, AgNP enters in lysosomes, avoid degradation and due to the acidic pH of lysosomes significantly generate high ROS levels. These data are further confirmed by the activation of different oxidative genes. Additionally, we demonstrated the biocompatibility of AgNP on mouse liver and ovarian organoids as an ex vivo model while AgNP showed the therapeutic efficacy on patient derived tumor organoids (PDTO).