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Dynamically enhancing plaque targeting via a positive feedback loop using multifunctional biomimetic nanoparticles for plaque regression. J Control Release 2019 Aug 28;308:71-85

Date

07/12/2019

Pubmed ID

31295543

DOI

10.1016/j.jconrel.2019.07.007

Scopus ID

2-s2.0-85068902207 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

A paradigm shift from preventive therapy to aggressive plaque regression and eventual eradication is much needed to address increasing atherosclerotic burden and risks. Herein, we report a biologically inspired dual-targeting multifunctional recombinant high-density lipoprotein (rHDL)-mimicking core-shell nanoplatform. It is composed of an ATP-responsive ternary polyplexes core for SR-A siRNA and catalase complexation, and a phosphatidylserine-modified rHDL-based outer shell for SR-BI and CD36 targeting, in which pitavastatin is packaged. We demonstrated that dual-targeting biomimetic core-shell nanoparticles dynamically enhanced macrophage CD36 targeting in the plaques by establishing a positive feedback loop via the reciprocal regulation of SR-A and CD36. Positive feedback-enabled accumulation of the nanoparticles in the atherosclerotic plaques increased by 3.3-fold following 4-week repeated administration. A 3-month dosage regimen of the dual-targeting rHDL-mimicking nanoparticles reduced plaque areas by 65.8%, and decreased macrophages by 57.3%. Collectively, this work shows that dynamically enhancing plaque targeting via a positive feedback loop and dual action of cholesterol deposition inhibition and efflux enhancement accomplished with our novel multifunctional biomimetic nanoparticles provides a new way to regress plaques and alleviate the atherosclerotic burden.

Author List

Jiang C, Qi Z, He W, Li Z, Tang Y, Wang Y, Huang Y, Zang H, Yang H, Liu J

Author

Hu Yang PhD Chair, Professor in the Biomedical Engineering department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Apolipoproteins E
Biomimetic Materials
CD36 Antigens
Feedback, Physiological
Lipoproteins, HDL
Macrophages
Male
Mice
Mice, Knockout
Nanoparticles
Plaque, Atherosclerotic
RAW 264.7 Cells
RNA, Small Interfering