Fine tuning of core-shell structure of hyaluronic acid/cell-penetrating peptides/siRNA nanoparticles for enhanced gene delivery to macrophages in anti-atherosclerotic therapy.

Fine tuning of core-shell structure of hyaluronic acid/cell-penetrating peptides/siRNA nanoparticles for enhanced gene delivery to macrophages in anti-atherosclerotic therapy. Biomacromolecules. 2018 Apr 11;: Authors: Zhao Y, He Z, Gao H, Tang H, He J, Guo Q, Zhang W, Liu J Abstract Hyaluronic acid (HA)-coated LOX-1 specific siRNA-condensed cell-penetrating peptides (CPPs) nanocomplexes were developed for targeted gene delivery to macrophages and suppression of lipid accumulation. The HA coating facilitated the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors and was further degraded by hyaluronidase (HAase) intra plaques for exposing the naked CPPs nanocomplexes (NCs) and achieving the ultimate location into macrophages. The surface coating of HA was verified by the increased particle size, inverted zeta potential, and TEM images. The targeting mechanism was studied on the established injured endothelium-macrophages co-culture system, which revealed that modification of higher molecular weight HA and higher HA coating density on NCs, termed as NPs-3, improved the intracellular uptake of nanoparticles by macrophages. Macrophages internalized NCs via caveolae-mediated endocytosis pathway. Moreover, NPs-3 exhibited better cellular drug efficacy in preventing macrophage-derived foam cells formation than other preparations. Compared with NCs, HA decoration showed enhanced atherosclerotic lesions targeting ...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research