Dynamically enhancing plaque targeting via a positive feedback loop using multifunctional biomimetic nanoparticles for plaque regression

Therapies Targeted at Non-Coding RNAs in Prevention and Limitation of Myocardial Infarction and Subsequent Cardiac Remodeling—Current Experience and Perspectives

“…An example is multifunctional biomimetic nanoparticle system (ternary polyplexes coated with ApoA-I resembling HDL particles), which not only interacts with specific receptors on macrophage, but also creates positive feedback loop which facilitates the drug delivery to the macrophage. Briefly, down-regulation of one receptor (SR-A on macrophages by siRNA released by the nanoparticle) results in enhancement of the other receptor activity (CD36), which furtherly promotes binding to macrophages and siRNA release into this cell [ 170 ]. Another method of drug delivery at specific site is a use of nanoplatforms targeted at different cells (like core-shell nanoparticles composed of PGLA core and three external layers: lipid layer, apoA-I layer for enhanced entry into macrophages, and hyaluronic acid layer for endothelial cell targeting) [ 171 ].…”

(r)HDL in theranostics: how do we apply HDL's biology for precision medicine in atherosclerosis management?

“…Among the molecules with therapeutic properties are statins, 113,114 LXR agonists, 103,115 bioactive lipids, 116 immunomodulators, 117 siRNA and miRNA molecules, [118][119][120] as well as preparations where more than one active component is combined. 121,122 For imaging applications, rHDL has been loaded with fluorescent dyes or quantum dots for optical imaging, 44,50,55,103,108,123,124 contrast agents as iron oxide or gadolinium for MRI, 50,113,123,125 radionuclides as zirconium-89 ( 89 Zr) for PET, 55,103,117 or goldbased rHDL for CT, 50,123,126 among others.…”

“…statins, immunomodulatory drugs or siRNA/miRNA molecules) and enhance their intrinsic efficacy, reducing in turn the side effects of the payloads. 113,117,122 On the other hand, other preparations sought to increase the residence time of rHDL-cargo in the system in order to increase the vector's therapeutic effect (e.g. rHDL PEGylation, LCAT inhibitors or cargo liberation controlling polymers) or improve/adapt its targeting capacity (e.g.…”

High density lipoprotein mimicking nanoparticles for atherosclerosis

“…In 2019, Liu and her coworkers designed another novel type of dual-targeting rHDL NPs to further enhance antiatherosclerotic efficacy. The dual-targeting rHDL NPs were composed of an adenosine triphosphate (ATP)responsive ternary polyplexes core, which was loaded with scavenger receptor A (SR-A) targeting siRNA for upregulating the CD36 receptors and oxygen-evolving catalase for accelerating the ATP production for rapid release of SR-A siRNA [47]. The outer shells of the dualtargeting rHDL NPs were modified with apoA-I and phosphatidylserine to target SR-BI and the CD36 receptors of the macrophages as well as carry pitavastatin (PT) to remove cholesterol and inhibit the engulfment of LDL by macrophages ( Fig.…”

“…In the same year, another study conducted by Liu and coworkers reported on the development of LT loaded spherical rHDL NPs, LT-s-rHDL NPs, and the effect of the LT:s-rHDL ratio on its anti-atherosclerotic effect. The authors showed that the NPs with the ratio of LT:s-rHDL of approximately 10 had the best synergistic effect in inhibiting ox-LDL uptake by macrophages in vitro and were able to reduce 24.9% of the plaque area in vivo compared to the control [47]. Similarly, in 2018, Chen and coworkers investigated the effect of monosialoganglioside (GM1) on the anti-atherogenic efficacy of LT-rHDL NPs.…”