Self-Assembled Peptide Nanostructures Targeting Death Receptor 5 and Encapsulating Paclitaxel As a Multifunctional Cancer Therapy

Tyson J. Moyer, Feng Chen, Daniel J. Toft, Yves Ruff, Vincent L. Cryns, Samuel I. Stupp

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)6046-6053
Number of pages8
JournalACS Biomaterials Science and Engineering
Volume5
Issue number11
DOIs
Publication statusPublished - Nov 11 2019

Keywords

  • TRAIL
  • death receptors
  • paclitaxel
  • peptide amphiphiles
  • supramolecular cancer therapies

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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