School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200240, China.
ACS Appl Mater Interfaces. 2020 Apr 22;12(16):18301-18308. doi: 10.1021/acsami.0c00650. Epub 2020 Apr 13.
The targeted nanoagents have shown great potential clinically for cancer therapy. Traditional targeted nanodrugs are usually prepared through surface postmodification. Herein, a nanodrug is self-assembled from the amphiphilic precursor of targeting peptide RGD conjugated with cytotoxin epothilone B (Epo B) through a linker containing the thioketal (tk) group that is sensitive to reactive oxygen species (ROS). The obtained RGD-tk-Epo B conjugate nanoparticles (RECNs) are stable and uniform, which facilitates improving tumor-targeting capacity and accumulation of the drug because of the large number of RGD on the surface of the RECN. After internalization by cancer cells, the blood-inert tk group between RGD and Epo B can be cleaved in the presence of high level of ROS to release Epo B, exhibiting a markedly tumor selectivity and excellent anticancer efficiency and .
靶向纳米制剂在癌症治疗的临床应用中显示出巨大的潜力。传统的靶向纳米药物通常通过表面后修饰来制备。本文通过连接子将靶向肽 RGD 与细胞毒素埃坡霉素 B（Epo B）偶联的两亲性前体自组装成纳米药物，该连接子含有对活性氧（ROS）敏感的硫缩酮（tk）基团。所得的 RGD-tk-Epo B 缀合物纳米粒（RECN）稳定且均匀，由于 RECN 表面有大量的 RGD，因此有利于提高肿瘤靶向能力和药物积累。进入癌细胞后，在高水平 ROS 的存在下，RGD 和 Epo B 之间的血液惰性 tk 基团可以被切割，从而释放 Epo B，表现出明显的肿瘤选择性和优异的抗癌效率。
