ROS-Responsive Nanoparticles Formed from RGD–Epothilone B Conjugate for Targeted Cancer Therapy
Xuelin Xia, Xiaoyuan Yang, Ping Huang, Deyue Yan
Abstract
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 in vitro and in vivo.