Open AccessSelf-Assembled Peptide Nanostructures Targeting Death Receptor 5 and Encapsulating Paclitaxel As a Multifunctional Cancer Therapy
Author(s) -
Tyson J. Moyer,
Feng Chen,
Daniel J. Toft,
Yves Ruff,
Vincent L. Cryns,
Samuel I. Stupp
Publication year - 2019
Publication title -
acs biomaterials science and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.082
H-Index - 50
ISSN - 2373-9878
DOI - 10.1021/acsbiomaterials.9b01259
Subject(s) - paclitaxel , peptide , in vivo , cancer cell , materials science , supramolecular chemistry , nanofiber , cancer research , in vitro , cancer , nanotechnology , chemistry , medicine , biochemistry , biology , molecule , microbiology and biotechnology , organic chemistry
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.