MESOPOROUS SILICA NANOPARTICLES FOR THE SELECTIVE DELIVERY OF DOXORUBICIN TO FOLATE RECEPTOR- EXPRESSING CANCER CELLS

Abstract

Breast and cervical cancers significantly impact women's health globally, with breast cancer accounting for approximately 2.3 million new cases annually. This highlights the urgent need for targeted therapeutic strategies that effectively eliminate tumor cells while preserving normal tissues. In this study, we developed a mesoporous silica-based nanodevice, FOL-MSN-DOXO, designed for the localized delivery of the chemotherapeutic agent doxorubicin (DOXO). This nanodevice utilizes the acidic tumor microenvironment for drug release via an acid-labile bond and incorporates folic acid (FOL) to enhance uptake by folate receptor-expressing cancer cells (FR+). The efficacy of FOL-MSN-DOXO was evaluated through various in vitro assays, including fluorescence-activated cell sorting (FACS), growth assays, and ROS measurements, as well as immunostaining of dorsal root ganglia (DRG) cells from neonatal rats. Our results demonstrate that FOL-MSN-DOXO effectively induces apoptosis in FR+ cancer cells (e.g., HeLa and T-47D), while exhibiting minimal toxicity towards FR3 normal cells (3T3-L1 and BJhTERT). Conversely, free DOXO exhibited significant toxicity across all tested cell lines. Notably, FOL-MSN-DOXO reduced neuronal toxicity compared to free DOXO, underscoring its neuroprotective potential. In summary, FOL-MSN-DOXO offers a promising targeted drug delivery system that selectively induces cytotoxicity in FR+ cancer cells while sparing normal tissues. This approach mitigates the neurotoxic effects associated with doxorubicin, highlighting the efficacy and safety of folic acid-functionalized mesoporous silica nanoparticles in cancer treatment.