Zhang Luzhong, Liu Fan, Li Guicai, Zhou Youlang, Yang Yumin
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China; Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong 226001, China.
J Pharm Sci. 2015 Dec;104(12):4185-4196. doi: 10.1002/jps.24649. Epub 2015 Sep 23.
One major obstacle in the application of drug delivery systems for cancer chemotherapy is their poor penetration in tumor tissues. Conjugating active ligand moieties to the surface of nanoparticles may be a promising approach for enhancing the tumor accumulation and penetration of nanoparticles. Herein, the cell-penetrating peptide twin-arginine translocation (Tat)-conjugated epirubicin-loaded poly(lactic-glycolic acid) nanoparticles were prepared to achieve deep tumor penetration. The morphology and size of nanoparticles were characterized by scanning electron microscopy and dynamic light scattering, and the biological behaviors of nanoparticles were evaluated. It is demonstrated that Tat-conjugated nanoparticles have a significant improvement in antitumor activity and biodistribution compared with nonconjugated nanoparticles. Importantly, Tat conjugated on the surface of nanoparticles could facilitate the encapsulated drug penetration into deeper tumor tissue. Additionally, Tat-conjugated nanoparticles have good biocompatibility, as demonstrated by hemolytic tests, in vitro cytotoxicity, and histology study. These results suggested that the Tat-conjugated nanoparticles, as a powerful delivery system for chemotherapeutic drug, would have a promising application in human cancer therapy.
药物递送系统应用于癌症化疗的一个主要障碍是其在肿瘤组织中的穿透性较差。将活性配体部分缀合到纳米颗粒表面可能是增强纳米颗粒在肿瘤中的积累和穿透的一种有前景的方法。在此，制备了细胞穿透肽双精氨酸转运（Tat）缀合的负载表柔比星的聚乳酸-羟基乙酸纳米颗粒，以实现肿瘤的深度穿透。通过扫描电子显微镜和动态光散射对纳米颗粒的形态和尺寸进行了表征，并评估了纳米颗粒的生物学行为。结果表明，与未缀合的纳米颗粒相比，Tat缀合的纳米颗粒在抗肿瘤活性和生物分布方面有显著改善。重要的是，缀合在纳米颗粒表面的Tat可以促进包封药物渗透到更深的肿瘤组织中。此外，溶血试验、体外细胞毒性试验和组织学研究表明，Tat缀合的纳米颗粒具有良好的生物相容性。这些结果表明，Tat缀合的纳米颗粒作为一种强大的化疗药物递送系统，在人类癌症治疗中具有广阔的应用前景。
