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 journal › Article

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
JournalACS Biomaterials Science and Engineering
DOIs
Publication statusAccepted/In press - Jan 1 2019

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TNF-Related Apoptosis-Inducing Ligand Receptors
Paclitaxel
Amphiphiles
Peptides
Nanostructures
Chemotherapy
Cell death
Cyclic Peptides
Nanofibers
Toxicity
Tumors
Cells

Keywords

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

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

Cite this

Self-Assembled Peptide Nanostructures Targeting Death Receptor 5 and Encapsulating Paclitaxel As a Multifunctional Cancer Therapy. / Moyer, Tyson J.; Chen, Feng; Toft, Daniel J.; Ruff, Yves; Cryns, Vincent L.; Stupp, Samuel I.

In: ACS Biomaterials Science and Engineering, 01.01.2019.

Research output: Contribution to journal › Article

Moyer, TJ, Chen, F, Toft, DJ, Ruff, Y, Cryns, VL & Stupp, SI 2019, 'Self-Assembled Peptide Nanostructures Targeting Death Receptor 5 and Encapsulating Paclitaxel As a Multifunctional Cancer Therapy', ACS Biomaterials Science and Engineering. https://doi.org/10.1021/acsbiomaterials.9b01259
Moyer TJ, Chen F, Toft DJ, Ruff Y, Cryns VL, Stupp SI. Self-Assembled Peptide Nanostructures Targeting Death Receptor 5 and Encapsulating Paclitaxel As a Multifunctional Cancer Therapy. ACS Biomaterials Science and Engineering. 2019 Jan 1. https://doi.org/10.1021/acsbiomaterials.9b01259
Moyer, Tyson J. ; Chen, Feng ; Toft, Daniel J. ; Ruff, Yves ; Cryns, Vincent L. ; Stupp, Samuel I. / Self-Assembled Peptide Nanostructures Targeting Death Receptor 5 and Encapsulating Paclitaxel As a Multifunctional Cancer Therapy. In: ACS Biomaterials Science and Engineering. 2019.
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