Folic Acid-Chitosan Conjugated Mesoporous Silica Nanoparticles for Enhanced Piceatannol Uptake in MCF‑7 Breast Cancer Cells

Targeted drug delivery using nanoparticle-based systems offers a promising strategy for improving breast cancer therapy. Mesoporous silica nanoparticles (MSNs) are attractive carriers due to their stability and ease of surface modification for attaching targeting ligands like folic acid. This study developed a folate receptor-mediated delivery system using functionalized MSNs loaded with piceatannol (PTL), a natural compound with known anticancer potential. MSNs were functionalized with 3-aminopropyltriethoxysilane (APTES) and succinic anhydride and then conjugated with a folic acid-chitosan (FA-CS) conjugate. This functionalization significantly enhanced not only PTL loading (44% vs 16% in bare MSNs) but also entrapment efficiency (89% vs 32%). Further, X-ray diffraction confirmed PTL remained amorphous within the MSNs, improving its aqueous solubility. Apart from this, the FA-CS conjugated MSNs demonstrated pH-sensitive, diffusion-controlled PTL release, with significantly higher release at acidic pH (88% at pH 5.5 in 2 h) compared to physiological pH (30% at pH 7.4). Subsequently, in vitro cellular studies on MCF-7 breast cancer cells confirmed a significantly enhanced cytotoxic and apoptotic effect with FA-CS conjugated PTL-loaded MSNs. This improved efficacy is attributed to increased cellular internalization mediated by the folic acid targeting moiety. These findings highlight the potential of FA-CS conjugated MSNs for the development of a targeted and effective delivery system for hydrophobic drugs like PTL for breast cancer treatment.