Folate-functionalized core–shell nanocarrier System for sustained and targeted delivery of <i>Saraca Indica</i> for breast cancer treatment

<b>Background:</b> Targeted therapy plays a crucial role in minimizing the adverse effects of chemotherapy on normal cells by specifically directing therapeutics to cancerous tissues. <b>Objectives:</b> The purpose of this study is to develop a novel nanocarrier system based on components that work in harmony to achieve dual-targeted and efficient breast cancer (BC) therapy. <b>Methods:</b> The nanocarrier was successfully prepared using pluronic acid (PL), sodium hyaluronate (SH), and folate-conjugated chitosan (CS-FA) as core-shell nanoparticles (NPs) for delivering anticancer agent; <i>Saraca Indica</i> (SI) extract. CS-FA was chemically synthesized and then combined with SH to form the NPs' shell, coating SI-loaded self-assembled PL nanomicelles core. <b>Results:</b> The core-shell SI-loaded NPs (SINPs) possess stable shell, as indicated by their zeta-potential of +48 ± 2.3 mV and size of 224 ± 2.0 nm. The SI's loading was 47.3%. <i>In-vitro</i> release profile of SI from SINPs was sustained for 20-days. The SI free form exhibited IC₅₀ of 41.29 ± 2.89 µg/ml, while SINPs showed 30.04 ± 2.14 µg/ml, which ascertains the role of encapsulating SI in NPs in improving its cytotoxicity against MCF-7 BC cells. Fluorescent micrographs indicated that (CS-FA)-based NPs were significantly engulfed by MCF-7 cells as compared to CS NPs, suggesting that CS-FA-based NPs have enhanced therapeutic efficacy through endocytosis-mediated by folate receptors. The SINPs significantly reduced tumor volume in mice compared to free SI, demonstrating their potent anticancer activity, and confirming that SINPs can increase the SI's anticancer efficiency <i>via</i> targeted folate receptor pathways. <b>Conclusion</b>: The developed SINPs are a promising targeted nano-delivery system for SI toward an augmented BC treatment.