Abstract
Targeted drug delivery systems offer a promising strategy to enhance the therapeutic index of chemotherapeutic agents while minimizing systemic toxicity. In this study, we developed hyaluronic acid-decorated mesoporous silica nanoparticles (HA-MSNs) for the target-specific delivery of doxorubicin (DOX) to CD44-overexpressing breast cancer cells. Mesoporous silica nanoparticles (MSNs) were synthesized via a sol-gel method, functionalized with amine groups, and subsequently conjugated with hyaluronic acid, which acts both as a targeting ligand for CD44 receptors and as a gatekeeper to prevent premature drug leakage. The successful synthesis and surface modification of HA-MSNs were confirmed using transmission electron microscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, and nitrogen adsorption-desorption isotherms. HA-MSNs exhibited a high drug loading capacity for DOX and demonstrated pH-dependent drug release behavior, with accelerated release under acidic conditions mimicking the tumor microenvironment. In vitro biological evaluations revealed that DOX-loaded HA-MSNs (DOX@HA-MSNs) exhibited significantly higher cellular uptake and cytotoxicity in CD44-overexpressing MDA-MB-231 breast cancer cells compared to CD44-deficient MCF-7 cells. Competitive inhibition assays with free hyaluronic acid confirmed that the cellular internalization of HA-MSNs was mediated by receptor-mediated endocytosis. These findings demonstrate that HA-MSNs are highly promising nanocarriers for targeted chemotherapy, offering a dual-responsive, receptor-specific platform for breast cancer treatment.
