Glycocalyx-Mimicking Nanoparticles with Differential Organ Selectivity for Drug Delivery and Therapy.

Organ-selective drug delivery is expected to maximize the efficacy of various therapeutic modalities while minimizing their systemic toxicity. Lipid nanoparticles and polymersomes can direct the organ-selective delivery of mRNAs or gene editing machineries, but their delivery has been limited to mostly liver, spleen, and lung. We urgently need a platform that enables delivery to these and other target organs. Here, we generate a library of glycocalyx-mimicking nanoparticles (GlyNPs) comprising five randomly combined sugar moieties and use direct in vivo library screening to identify GlyNPs with preferential biodistribution in liver, spleen, lung, kidneys, heart, and brain. Each organ-targeting GlyNP hit show cellular tropism within the organ. Liver, kidney, and spleen-targeting GlyNP hits equipped with therapeutics effectively can alleviate the symptoms of acetaminophen-induced liver injury, cisplatin-induced kidney injury, and immune thrombocytopenia in mice, respectively. Furthermore, the differential organ targeting of GlyNP hits is influenced not by the protein corona but by the sugar moieties displayed on their surface. We envision that our GlyNP-based platform may enable the organ- and cell-targeted delivery of therapeutic cargoes. This article is protected by copyright. All rights reserved.