Biotinylated Self-Assembled Cytarabine Nano-Prodrug with Enhanced Targetability and Anticancer Efficacy: An In Vitro Study.

In this study, we developed a tumor-target biotinylated cytarabine (Ara-C) prodrug linked through a disulfide bond (Bio-SS-Ara). To enhance its delivery, Bio-SS-Ara was found to be able to self-assemble into uniform nanoparticles (BSSA NPs) with an average particle size of 230 nm, a PDI of 0.265, a critical micelle concentration (CMC) of 5.89 μg/mL, and a zeta potential of -15 mV. BSSA NPs showed good storage stability over 6 weeks. In a glutathione-rich environment, the drug release of BSSA NPs was more rapid than that of BCCA NPs. Concentration-dependent size analysis suggested that BSSA NPs were formed through a dynamic, reversible assembly process. Cellular uptake studies showed significantly increased internalization of BSSA NPs compared to free Ara-C, with enhancements of 4.13-fold in HeLa cells and 3.13-fold in A549 cells. Cytotoxicity assays demonstrated enhanced efficacy, reducing the IC50 by 67.9% in HeLa and 45.2% in A549 cells. The migration rate of HeLa cells was reduced to 14% after BSSA NPs treatment, in comparison with Ara-C treatment, and nuclear shrinkage and fragmentation were observed, indicating the potential of BSSA NPs to limit tumor progression and induce apoptosis. Importantly, no hemolysis was observed in BSSA NPs-treated groups, confirming their good biocompatibility. These findings suggest that BSSA NPs represent a promising strategy for targeted cancer therapy, combining enhanced drug delivery, antitumor efficacy, and biocompatibility.