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Self‐Assembled Peptide Amphiphile Nanofibers for Controlled Therapeutic Delivery to the Atherosclerotic Niche
Author(s) -
Peters Erica B.,
Karver Mark R.,
Sun Kui,
Gillis David C.,
Biswas Suvendu,
Clemons Tristan D.,
He Wenhan,
Tsihlis Nick D.,
Stupp Samuel I.,
Kibbe Melina R.
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202100103
Subject(s) - abca1 , liver x receptor , nanofiber , chemistry , nanocarriers , microbiology and biotechnology , reactive oxygen species , pharmacology , cancer research , drug delivery , biochemistry , biology , nanotechnology , materials science , transporter , nuclear receptor , organic chemistry , transcription factor , gene
Atherosclerotic plaque remains the leading contributor to cardiovascular disease and requires invasive surgical procedures for its removal. Nanomedicine offers a minimally invasive approach to alleviate plaque burden by targeted therapeutic delivery. However, nanocarriers are limited without the ability to sense and respond to the diseased microenvironment. In this study, targeted self‐assembled peptide amphiphile (PA) nanofibers are developed that cleave in response to biochemical cues expressed in atherosclerotic lesions—reactive oxygen species (ROS) and intracellular glutathione—to deliver a liver X receptor agonist (LXR) to enhance macrophage cholesterol efflux. The PAs release LXR in response to physiological levels of ROS and reducing agents and can be co‐assembled with plaque‐targeting PAs to form nanofibers. The resulting LXR PA nanofibers promoted cholesterol efflux from macrophages in vitro as well as LXR alone and with lower cytotoxicity. Further, the ApoA1‐LXR PA nanofibers target plaque within an atherosclerotic mouse model in vivo and activate ATP‐binding cassette A1 (ABCA1) expression as well as LXR alone with reduced liver toxicity. Taken together, these results demonstrate the potential of self‐assembled PA nanofibers for controlled therapeutic delivery to the atherosclerotic niche.