Nanoparticle targeting and cholesterol flux through scavenger receptor type B-1 inhibits cellular exosome uptake

Michael P. Plebanek, R. Kannan Mutharasan, Olga Volpert, Alexandre Matov, Jesse C. Gatlin, C. Shad Thaxton*

*Corresponding author for this work

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Article number15724
JournalScientific reports
Volume5
DOIs
StatePublished - Oct 29 2015

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Exosomes
Scavenger Receptors
Nanoparticles
Cholesterol
HDL Lipoproteins
Lipids
Membrane Microdomains
HDL Cholesterol
Cluster Analysis
Cell Membrane

ASJC Scopus subject areas

  • General

Cite this

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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.",
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Nanoparticle targeting and cholesterol flux through scavenger receptor type B-1 inhibits cellular exosome uptake. / Plebanek, Michael P.; Mutharasan, R. Kannan; Volpert, Olga; Matov, Alexandre; Gatlin, Jesse C.; Thaxton, C. Shad.

In: Scientific reports, Vol. 5, 15724, 29.10.2015.

Research output: Contribution to journalArticle

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AU - Plebanek, Michael P.

AU - Mutharasan, R. Kannan

AU - Volpert, Olga

AU - Matov, Alexandre

AU - Gatlin, Jesse C.

AU - Thaxton, C. Shad

PY - 2015/10/29

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