Twin-Arginine Translocation Peptide Conjugated Epirubicin-Loaded Nanoparticles for Enhanced Tumor Penetrating and Targeting
Twin-Arginine Translocation Peptide Conjugated Epirubicin-Loaded Nanoparticles for Enhanced Tumor Penetrating and Targeting
复制标题
双精氨酸易位肽缀合负载表阿霉素的纳米颗粒，用于增强肿瘤穿透和靶向。
DOI：
10.1002/jps.24649
复制
发表时间：
2015-12-01
影响因子：
3.8
通讯作者：
Yang, Yumin
中科院分区：
文献类型：
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作者：
Zhang, Luzhong;Liu, Fan;Yang, Yumin
癌症化疗药物递送系统应用中的一个主要障碍是其在肿瘤组织中的渗透性差。将活性配体部分连接到纳米粒子表面可能是一种有前景的提高纳米粒子在肿瘤中聚集和渗透的方法。在此，制备了细胞穿透肽双精氨酸转位（Tat）共轭的载表柔比星聚乳酸 - 羟基乙酸共聚物纳米粒子以实现肿瘤深部渗透。通过扫描电子显微镜和动态光散射对纳米粒子的形态和尺寸进行了表征，并对纳米粒子的生物学行为进行了评估。结果表明，与未共轭的纳米粒子相比，Tat共轭纳米粒子在抗肿瘤活性和生物分布方面有显著改善。重要的是，连接在纳米粒子表面的Tat能够促进包封药物渗透到更深的肿瘤组织中。此外，溶血试验、体外细胞毒性和组织学研究表明，Tat共轭纳米粒子具有良好的生物相容性。这些结果表明，Tat共轭纳米粒子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良好的应用前景。（C）2015威利期刊公司和美国药剂师协会
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.