Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 16, Pages 18301-18308Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c00650
Keywords
epothilone B; drug delivery; ROS-responsive; self-assemble; targeted cancer therapy
Funding
- National key research and development plan of P. R. China [2016YFA0201500]
- National Natural Science Foundation of China [21702097, 21504055, 91527304]
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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.
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