Next Article in Journal
Polymer-Based Nanocarriers for Co-Delivery and Combination of Diverse Therapies against Cancers
Previous Article in Journal
Improved Anticancer Effect of Magnetite Nanocomposite Formulation of GALLIC Acid (Fe3O4-PEG-GA) Against Lung, Breast and Colon Cancer Cells
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Nanomaterials 2018, 8(2), 84; https://doi.org/10.3390/nano8020084

Nanotherapeutics Containing Lithocholic Acid-Based Amphiphilic Scorpion-Like Macromolecules Reduce In Vitro Inflammation in Macrophages: Implications for Atherosclerosis

1
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA
2
Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA
3
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA
4
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08854, USA
5
Department of Chemistry, University of California-Riverside, Riverside, CA 92521, USA
*
Author to whom correspondence should be addressed.
Received: 28 December 2017 / Revised: 24 January 2018 / Accepted: 30 January 2018 / Published: 2 February 2018
Full-Text   |   PDF [1787 KB, uploaded 2 February 2018]   |  

Abstract

Previously-designed amphiphilic scorpion-like macromolecule (AScM) nanoparticles (NPs) showed elevated potency to counteract oxidized low-density lipoprotein (oxLDL) uptake in atherosclerotic macrophages, but failed to ameliorate oxLDL-induced inflammation. We designed a new class of composite AScMs incorporating lithocholic acid (LCA), a natural agonist for the TGR5 receptor that is known to counteract atherosclerotic inflammation, with two complementary goals: to simultaneously decrease lipid uptake and inhibit pro-inflammatory cytokine secretion by macrophages. LCA was conjugated to AScMs for favorable interaction with TGR5 and was also hydrophobically modified to enable encapsulation in the core of AScM-based NPs. Conjugates were formulated into negatively charged NPs with different core/shell combinations, inspired by the negative charge on oxLDL to enable competitive interaction with scavenger receptors (SRs). NPs with LCA-containing shells exhibited reduced sizes, and all NPs lowered oxLDL uptake to <30% of untreated, human derived macrophages in vitro, while slightly downregulating SR expression. Pro-inflammatory cytokine expression, including IL-1β, IL-8, and IL-10, is known to be modulated by TGR5, and was dependent on NP composition, with LCA-modified cores downregulating inflammation. Our studies indicate that LCA-conjugated AScM NPs offer a unique approach to minimize atherogenesis and counteract inflammation. View Full-Text
Keywords: atherosclerosis; amphiphile; TGR5; lithocholic acid; nanoparticle; inflammation; macrophages atherosclerosis; amphiphile; TGR5; lithocholic acid; nanoparticle; inflammation; macrophages
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Moretti, A.; Li, Q.; Chmielowski, R.; Joseph, L.B.; Moghe, P.V.; Uhrich, K.E. Nanotherapeutics Containing Lithocholic Acid-Based Amphiphilic Scorpion-Like Macromolecules Reduce In Vitro Inflammation in Macrophages: Implications for Atherosclerosis. Nanomaterials 2018, 8, 84.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Nanomaterials EISSN 2079-4991 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top