Engineered Polymeric Nanovector for Intracellular Peptide Delivery in Antitumor Therapy.

Objective: This study aimed to deliver a polypeptide from the Bax-BH3 domain (BHP) through the synthesis of self-assembled amphiphile nanovectors (NVs) and to assess their potential for cancer therapeutic applications and biological safety in vitro and in vivo. These findings provide valuable options for cancer intervention and a novel approach for the rational design of therapeutics. Methods: We studied the antitumor activity of BHP by preparing RGDfK-PHPMA-b-Poly (MMA- Results: NVs were successfully prepared with hydrated particle sizes ranging from 189.6 nm to 256.6 nm, spherical overall, and were able to remain stable in different media for 72 h with drug loading up to 15.2%. The NVs were be successfully internalized within 6 h with good biocompatibility. Neither BHP nor NV showed significant toxicity when administered alone, however, BHP-NV demonstrated significant side effects in vitro and in vivo. The apoptosis rate increased significantly from 14.13% to 66.34%. Experiments in vivo showed that BHP-NV exhibited significant apoptotic and tumor-suppressive effects. Conclusion: A targeted fluorescent NV with high drug delivery efficiency and sustained release protected the active center of BHP, constituting BHP-NV for targeted delivery. RPPMMRA demonstrated excellent biocompatibility, stability, and drug loading ability, whereas and BHP-NV demonstrated potent antitumor effects in vivo and in vitro.