Glycosylation Engineered Platelet Membrane Coated Nanoparticle For Targeted Inhibition Of Vascular Restenosis

Introduction: IL10 nanoparticles coated with platelet membrane (IL10-PNP) has good targeting and local immune regulation function, and hence can effectively reduce restenosis after vascular injury. However, IL10-PNP still accumulated in the liver and spleen in a significant amount. Consequently, it is imperative that present PNP be further improved in terms of their immune-compatibility and targeting abilities. Glycosylation is one of the most important post-translational modifications of proteins, and platelet function is closely related to surface glycosylation. Hypothesis: We assessed the hypothesis that glycosylation engineered IL10-PNP (IL10-GE-PNP) with surface sialic acid removed and fucose conjunct has better biocompatibility and target ability. Methods: Glycosylation engineer of platelet membrane glycoprotein was performed by treating with neuraminidase and adding GDP-Fucose, fucosyltransferase I and fucosyltransferase VII. IL10 nanoparticles were prepared by recombinant IL-10 and PLGA nanoparticles and then coated by a glycosylation engineered platelet membrane. In vitro experiments were carried out to verify that glycosylation engineering of IL10-PNP enhanced the binding ability and regulation function of macrophages, smooth muscle cells (SMCs) and endothelial cells (ECs). In vivo experiments were carried out in a carotid artery injury model to verify the effect on reducing deposition in liver and spleen and ameliorating vascular restenosis. Results: The above methods could effectively remove sialic acids and add α (1,2)-fucose and α (1,3)-fucose. IL10-GE-PNP was successfully constructed and demonstrated its ability to target and regulate macrophage polarization in vitro and in vivo. The regulation of macrophages by IL10-GE-PNP can reduce the proliferation and migration of SMCs and promote the repair of ECs in an inflammatory environment both in vitro and in vivo, thereby reducing restenosis after vascular injury. And glycosylation engineer significantly reduces the deposition in liver and spleen of IL10-PNP. Conclusions: In conclusion, IL10-GE-PNP is an excellent candidate for targeting vascular injury and holds promise as an innovative drug delivery system for suppressing vascular restenosis.