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Abstract
<title>Abstract</title> <p>A significant challenge in drug delivery is developing multifunctional nanocarriers that can navigate complex, infection-prone pathological microenvironments. This study presents the design and physicochemical enhancement of a hybrid inorganic nanoplatform achieved by incorporating silver nanoparticles into mesoporous silica nanoparticles (MSNPs) via a surfactant-templated approach, followed by amine functionalization and in situ Ag⁺ reduction. Ag-MSNPs@Cipro were synthesized by successfully encapsulating Ciprofloxacin (Cipro) within the structured framework. Comprehensive structural and textural analyses (TEM, SEM, EDX, BET, UV-Vis, XRD, FTIR, and DSC) confirmed the effective incorporation of silver, a consistent spherical morphology, and the maintenance of a recognizable mesoporous architecture with a pore size of around 3.4 nm. The hybrid nanoformulation exhibits a robust, pH-responsive drug release profile, showing regulated stability at physiological pH 7.4 with a cumulative release of 9.05% and fast cargo release at acidic pH 5.5 with a release of 47.15% after 96 hours. This dynamic behavior enables customized distribution to specified sites while minimizing early cargo leakage. The system demonstrates significant, dose-dependent DPPH radical scavenging efficacy due to the structural synergy between the Ag-enhanced framework and the silica matrix. Microbiological evaluations revealed enhanced antibacterial efficacy against Escherichia coli, Staphylococcus aureus, Candida albicans, and Aspergillus niger as compared to free Cipro or unloaded Ag-MSNPs, with significantly lower minimum inhibitory concentrations (MICs). Additionally, compared to free Cipro, in vitro cytotoxicity tests demonstrated strong antiproliferative activity against MCF7 breast and A549 lung cancer cell lines, with IC•₀ values of 1.95 µg/mL and 1.86 µg/mL, respectively. This increased effectiveness is due to typical apoptotic mechanisms, such as cell shrinkage and membrane blebbing, as observed under inverted microscopy. Overall, these results show that the Ag-MSNPs@Cipro platform effectively combines pH-responsive dual therapeutic action with structural stability, providing a viable method to get beyond the drawbacks of traditional administration routes in nanomedicine.</p>