Abstract
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.
Original language | English |
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Pages (from-to) | 6046-6053 |
Number of pages | 8 |
Journal | ACS Biomaterials Science and Engineering |
Volume | 5 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 11 2019 |
Keywords
- TRAIL
- death receptors
- paclitaxel
- peptide amphiphiles
- supramolecular cancer therapies
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering