用于抗肿瘤治疗中细胞内肽类药物递送的工程聚合纳米载体。

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--(Rhob-MA)) (RPPMMRA) and encapsulating it in BHP-NV. We also performed a series of characterizations and property analyses of RPPMMRA, including its size, stability, and drug-carrying capacity. The biocompatibility of RPPMMRA was evaluated in terms of cytotoxicity and hemolytic effects. The pro-apoptotic capacity of BHP was evaluated in vitro using mitochondrial membrane potential, flow cytometry, and apoptosis visualization techniques. The potential therapeutic effects of BHP on tumors were explored using reverse molecular docking. We also investigated the in vivo proapoptotic effect of BHP-NV in a nude mouse tumor model. 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.

目的：本研究旨在通过合成自组装两亲性纳米载体（NVs）递送 Bax-BH3 结构域（BHP）多肽，并评估其在体外和体内用于癌症治疗应用和生物安全性的潜力。这些发现为癌症干预提供了有价值的选择，并为治疗药物的合理设计提供了新方法。

方法：我们通过制备 RGDfK-PHPMA-b-Poly（MMA-（Rhob-MA））（RPPMMRA）并将其包裹在 BHP-NV 中，研究了 BHP 的抗肿瘤活性。我们还对 RPPMMRA 的一系列特性和性质进行了分析，包括其粒径、稳定性和载药能力。通过细胞毒性和溶血实验评估 RPPMMRA 的生物相容性。通过线粒体膜电位、流式细胞术和凋亡可视化技术评估 BHP 的促凋亡能力。通过反向分子对接研究了 BHP 对肿瘤的潜在治疗效果。我们还在裸鼠肿瘤模型中研究了 BHP-NV 的体内促凋亡作用。

结果：成功制备了水合粒径为 189.6nm 至 256.6nm 的 NVs，总体呈球形，在不同介质中 72h 内保持稳定，载药量高达 15.2%。NVs 在 6h 内成功内化，具有良好的生物相容性。单独使用 BHP 或 NV 时均无明显毒性，但 BHP-NV 表现出明显的体外和体内副作用。凋亡率从 14.13%显著增加至 66.34%。体内实验表明，BHP-NV 具有显著的凋亡和肿瘤抑制作用。

结论：一种具有高效药物传递效率和持续释放的靶向荧光 NV 保护了 BHP 的活性中心，构成了用于靶向递送的 BHP-NV。RPPMMRA 表现出优异的生物相容性、稳定性和载药能力，而 BHP-NV 在体内和体外均表现出强大的抗肿瘤作用。