Dynamically Enhancing Plaque Targeting Via a Positive Feedback Loop using Multifunctional Biomimetic Nanoparticles for Plaque Regression
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.
C. Jiang et al., "Dynamically Enhancing Plaque Targeting Via a Positive Feedback Loop using Multifunctional Biomimetic Nanoparticles for Plaque Regression," Journal of Controlled Release, vol. 308, pp. 71 - 85, Elsevier B.V., Aug 2019.
The definitive version is available at https://doi.org/10.1016/j.jconrel.2019.07.007
Chemical and Biochemical Engineering
Center for Research in Energy and Environment (CREE)
Keywords and Phrases
Atherosclerosis; Dual-targeting; Nanocarrier; Plaque regression; Plaque targeting; Positive feedback loop
International Standard Serial Number (ISSN)
Article - Journal
© 2019 Elsevier B.V., All rights reserved.
28 Aug 2019