Biomimetic MicroRNAs-Selenium-Nanocomposites for Targeted and Combined Hyperlipidemia Therapy.

Hyperlipidemia is considered as a high-risk factor for leading to type 2 diabetes mellitus and coronary heart disease, and with a significant decrease in blood selenium (Se) concentration in patients. MicroRNA-148a-3p (miR-148a-3p) inhibitor is a new and potential therapeutic target to bind low-density lipoprotein cholesterol receptors (LDLR) for decreasing the levels of low-density lipoprotein cholesterol in plasma. However, the therapeutics effects are not ideal in clinical translation of nucleic acids treatment, owing to the instability of the structure and short circulation time in vivo. Therefore, a platelet membrane (PM) cloaked Se nanoparticles (SeNPs) biomimetic delivery system with chitosan (CS) modified and miR-148a-3p inhibitors encapsulated is designed (PM/CS-SeNPs/miR). The PM/CS-SeNPs/miR show a uniform shell-core structure and spherical shape with a particle size of about 90 nm, which has great antioxidant function and ability to control blood lipids in vitro and in vivo. Co-delivering miR-148a-3p inhibitors and Se effectively alleviate hyperlipidemia via miR-148a-3p/LDLR pathway and Toll-Like Receptor 4 (TLR-4)/NF-κB signaling pathway, respectively. Furthermore, coated by PM, PM/CS-SeNPs/miR successfully prolong circulation time to 48 h in vivo and quickly target to liver with no toxicity. This dual combination therapy with miRNAs and Se based on nanoparticles targeted delivery presents a high-performance strategy precise hyperlipidemia treatment. This article is protected by copyright. All rights reserved.