期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 5, 期 11, 页码 6046-6053出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.9b01259
关键词
TRAIL; peptide amphiphiles; supramolecular cancer therapies; paclitaxel; death receptors
资金
- Center of Cancer Nano technology Excellence Grant [5U54CA151880-03]
- Breast Cancer Research Foundation
- Department of Defense Breast Cancer Research Program [W81XWH-10-1-0503]
- National Science Foundation
The development of tumor-targeted nanoscale carriers for the delivery of cancer therapeutics offers the ability to increase efficacy while limiting off-target toxicity. In this work, we focused on targeting death receptor 5 (DR5), which is highly expressed by cancer cells and, upon binding, triggers programmed cell death. Hence, a nanostructure targeting DR5 would act as a dual targeting and therapeutic agent. We report here on a peptide amphiphile (PA) containing a dimeric, cyclic peptide that self-assembles into cylindrical supramolecular nanofibers and targets DR5. Coassembly of the DR5-targeting PA and a pegylated PA creates a supramolecular nanoscale construct with enhanced binding affinity to DR5 relative to a monomeric targeting PA and was found to be cytotoxic in vitro. When combined with the chemotherapy paclitaxel, DR5-targeting carriers showed potent antitumor activity in vivo, demonstrating the multifunctional capabilities of peptide-based supramolecular nanostructures.
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