Folic acid–loaded amino-functionalized MCM-41 as a drug delivery system for cervical cancer modulating apoptotic and survival signals

Cervical cancer remains one of the most prevalent gynecological malignancies worldwide, with high mortality rates particularly in developing countries, necessitating the development of effective and targeted therapeutic strategies. In this study, a folic acid (FA)-loaded amino-functionalized MCM-41 mesoporous silica nanocarrier was developed as a controlled delivery platform for cervical cancer applications. Pure MCM-41 was synthesized via a precipitation method and subsequently functionalized with aminopropyl groups through post-synthesis grafting, followed by FA-loading. Structural, textural and morphological analyses confirmed successful functionalization while maintaining the ordered mesoporous framework. In vitro drug release studies demonstrated pH-responsive behavior, with enhanced folic acid release under physiological conditions (pH 7.4) compared to acidic conditions (pH 1.5), supporting its suitability for controlled delivery applications. Cytotoxicity evaluation using HeLa cervical cancer cells and WI38 normal fibroblasts revealed selective anticancer activity of FA-functionalized systems with minimal toxicity toward normal cells. Among all formulations, the DMSO-based FA-loaded MCM-41 exhibited the highest cytotoxic and apoptotic effects, comparable to Doxorubicin. Mechanistic studies indicated that treatment induced oxidative stress through increased nitric oxide and malondialdehyde levels, accompanied by depletion of antioxidant enzymes (SOD and GSH). Additionally, apoptosis induction was confirmed by an increased Bax/Bcl-2 ratio and activation of the intrinsic mitochondrial pathway, along with suppression of PI3K/AKT survival signaling, along with downregulation of p-AKT. In conclusion, the developed FA-loaded amino-functionalized MCM-41 nanocarrier demonstrates efficient tumor targeting, controlled drug release, and potent apoptosis-mediated anticancer activity, highlighting its potential as a promising platform for cervical cancer therapy.