HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

Abstract

High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers.

• Authors: Brenda L Sanchez-Gaytan, Francois Fay, Mark E Lobatto, Jun Tang, Mireille Ouimet, YongTae Kim, Susanne E M van der Staay, Sarian M van Rijs, Bram Priem, Liangfang Zhang, Edward A Fisher, Kathryn J Moore, Robert Langer, Zahi A Fayad, Willem J M Mulder
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 26 Issue 3 Pg. 443-51 (Mar 18 2015) ISSN: 1520-4812 [Electronic] United States
• PMID: 25650634 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Lipoproteins, HDL
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid

Topics

• Animals
• Biomimetic Materials (administration & dosage, chemistry, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Drug Delivery Systems (methods)
• Human Umbilical Vein Endothelial Cells
• Humans
• Lactic Acid (administration & dosage, chemistry, metabolism)
• Lipoproteins, HDL (administration & dosage, chemistry, metabolism)
• Macrophages (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Knockout
• Nanoparticles (administration & dosage, chemistry, metabolism)
• Plaque, Atherosclerotic (drug therapy, metabolism, pathology)
• Polyglycolic Acid (administration & dosage, chemistry, metabolism)
• Polylactic Acid-Polyglycolic Acid Copolymer