Dynamically enhancing plaque targeting via a positive feedback loop using multifunctional biomimetic nanoparticles for plaque regression
| Autor: | Jianping Liu, Cuiping Jiang, Zitong Qi, Haojing Zang, Yunbo Wang, Yuqi Tang, Zhuoting Li, Yilei Huang, Wanhua He, Hu Yang |
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| Rok vydání: | 2019 |
| Předmět: |
CD36 Antigens
Male CD36 Pharmaceutical Science 02 engineering and technology Mice 03 medical and health sciences Adenosine Triphosphate Apolipoproteins E Biomimetic Materials medicine Animals Macrophage RNA Small Interfering Pitavastatin 030304 developmental biology Positive feedback Feedback Physiological Mice Knockout 0303 health sciences biology Chemistry Macrophages Plaque regression Biomimetic nanoparticles 021001 nanoscience & nanotechnology Plaque Atherosclerotic Cell biology RAW 264.7 Cells biology.protein Nanoparticles Efflux Nanocarriers Lipoproteins HDL 0210 nano-technology medicine.drug |
| Zdroj: | Journal of Controlled Release. 308:71-85 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2019.07.007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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