Journal
CHEMMEDCHEM
Volume 9, Issue 7, Pages 1403-1412Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201400067
Keywords
chemotherapy; drug discovery; EphA2; ephrins; targeted delivery
Categories
Funding
- US National Institutes of Health (NIH) [CA138390, CA168517]
- US National Foundation for Cancer Research (NFCR)
Ask authors/readers for more resources
Because of its overexpression in a range of solid tumors, the EphA2 receptor is a validated target for cancer therapeutics. We recently described a new targeted delivery system based on specific EphA2-targeting peptides conjugated with the chemotherapeutic agent paclitaxel. Here, we investigate the chemical determinants responsible for the stability and degradation of these agents in plasma. Introducing modifications in both the peptide and the linker between the peptide and paclitaxel resulted in drug conjugates that are both long-lived in rat plasma and that markedly decrease tumor size in a prostate cancer xenograft model compared with paclitaxel alone treatment. These studies identify critical rate-limiting degradation sites on the peptide-drug conjugates, enabling the design of agents with increased stability and efficacy. These results provide support for our central hypothesis that peptide-drug conjugates targeting EphA2 represent an innovative and potentially effective strategy to selectively deliver cytotoxic drugs to cancer cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available