Design and optimization of Pt@ZIF-8 nanostructures via QbD approach: structural characterization and cytotoxic...

Platinum nanoparticles (Pt NPs) exhibit inherent anticancer properties; however, their therapeutic application is limited by poor colloidal stability, ineffective cellular uptake, and inconsistent formulation reproducibility. While zeolitic imidazolate framework-8 (ZIF-8) has shown promise as a pH-responsive nanocarrier, thorough optimization of Pt-encapsulated ZIF-8 (Pt@ZIF-8) nanostructures guided by Quality by Design (QbD) principles, as well as a mechanistic assessment of their biological effectiveness, remains insufficiently addressed. In this research, Pt@ZIF-8 nanoparticles were fabricated using a QbD strategy based on a central composite design to elucidate the relationships between formulation parameters and essential quality attributes. The optimized formulation exhibited nanoscale particle sizes, stable colloidal behavior, and effective integration of platinum into the ZIF-8 structure. Compared with uncoated Pt nanoparticles, Pt@ZIF-8 exhibited improved cellular uptake and greater anticancer efficacy against human cancer cells. Investigation revealed that oxidative stress induced cell death is associated with high ROS levels inside cells, low reduced glutathione concentration, low superoxide dismutase activity, and apoptosis. Overall, this study provides an optimization and mechanistic rationale to synthesize the Pt@ZIF-8 nanoparticles and provides a rationale to design a multi-functional MOF-based nanomedical system for cancer therapy.