@article{8a884386d8204d28a207600a8e164f49,
title = "Nanoparticle targeting and cholesterol flux through scavenger receptor type B-1 inhibits cellular exosome uptake",
abstract = "Exosomes are nanoscale vesicles that mediate intercellular communication. Cellular exosome uptake mechanisms are not well defined partly due to the lack of specific inhibitors of this complex cellular process. Exosome uptake depends on cholesterol-rich membrane microdomains called lipid rafts, and can be blocked by non-specific depletion of plasma membrane cholesterol. Scavenger receptor type B-1 (SR-B1), found in lipid rafts, is a receptor for cholesterol-rich high-density lipoproteins (HDL). We hypothesized that a synthetic nanoparticle mimic of HDL (HDL NP) that binds SR-B1 and removes cholesterol through this receptor would inhibit cellular exosome uptake. In cell models, our data show that HDL NPs bind SR-B1, activate cholesterol efflux, and attenuate the influx of esterified cholesterol. As a result, HDL NP treatment results in decreased dynamics and clustering of SR-B1 contained in lipid rafts and potently inhibits cellular exosome uptake. Thus, SR-B1 and targeted HDL NPs provide a fundamental advance in studying cholesterol-dependent cellular uptake mechanisms.",
author = "Plebanek, {Michael P.} and Mutharasan, {R. Kannan} and Olga Volpert and Alexandre Matov and Gatlin, {Jesse C.} and Thaxton, {C. Shad}",
note = "Funding Information: CST thanks the Howard Hughes Medical Institute (HHMI) for a Physician Scientist Early Career Award, the Department of Defense/Air Force Office of Scientific Research (FA95501310192), and the National Institutes of Health/National Cancer Institute (U54CA151880 and R01CA167041). AM thanks the National Cancer Institute (F32CA177104). MP thanks the Robert H. Lurie Comprehensive Cancer Center for the Fishel Fellowship for cancer research. JCG thanks the Pew Charitable Trusts for a Pew Biomedical Scholar Award and the National Institute of General Medical Sciences (R01GM102428) and Wyoming INBRE P20GM103432. We also thank the Northwestern University Nikon Imaging Center for assistance with microscopy and the Robert H. Lurie Comprehensive Cancer Center Flow Core for assistance with flow cytometry. The GFP-SR-B1 plasmid was a generous gift from Sirano Dhe-Paganon of the Dana Farber Cancer Institute.",
year = "2015",
month = oct,
day = "29",
doi = "10.1038/srep15724",
language = "English (US)",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}