Abstract
Targeted chemotherapeutic delivery systems capable of discriminating between cancerous and healthy tissues remain a cornerstone in advancing precision oncology. In this study, we report the design, synthesis, and evaluation of a smart, dual-functionalized mesoporous silica nanoparticle (MSN) system engineered for pH-triggered release and cell-specific delivery of Doxorubicin (DOX) to breast cancer cells. Spherical MSNs (~100 nm) were synthesized via a modified sol-gel method, loaded with DOX, and capped with an acid-labile polymeric gating framework linked via hydrazone bonds to prevent premature drug leakage. The particle surface was subsequently conjugated with MUC1-targeting aptamers to facilitate specific recognition of MUC1-overexpressing breast adenocarcinoma cells (MCF-7). Characterization via TEM, DLS, BET, and FTIR confirmed the mesoporous architecture, high specific surface area (~920 m²/g), and successful chemical modification. In vitro drug release studies demonstrated exceptional pH responsiveness: less than 12% of DOX was released at physiological pH (7.4) over 48 hours, whereas over 80% was rapidly discharged under acidic endosomal conditions (pH 5.0). Confocal laser scanning microscopy verified receptor-mediated internalization in MUC1-positive MCF-7 cells compared to non-targeted controls. Cytotoxicity assays revealed significantly enhanced antiproliferative activity against breast cancer cells while minimizing damage to healthy epithelial cells (MCF-10A). Overall, this targeted MSN platform offers a promising therapeutic strategy for precision breast cancer therapy with minimized off-target toxicity.
