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Adv. Mater., Mar 15 2024, | https://doi.org/10.1002/adma.202311283 Glycocalyx-Mimicking Nanoparticles with Differential Organ Selectivity for Drug Delivery and Therapy

Dohyeon Kim^1,2, Chang-Hee Whang ^1,2, Jungwoo Hong ^3,4, Monica Celine Prayogo ^1,2, Wonsik Jung ^1,2, Seojung Lee ^1,2, Hocheol Shin ^1,2, Yujin Kim ^1,2, Jiyoung Yu ^5,6, Min Joong Kim ^5,6, Kyunggon Kim^5,6, Hee-Seung Lee ^3,4, Sangyong Jon^1,2

¹Department of Biological Sciences, KAIST Institute of BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea.

²Center for Precision Bio-Nanomedicine, KAIST, 291 Daehak-ro, Daejeon, 34141, Republic of Korea.

³Department of Chemistry, KAIST, 291 Daehak-ro, Daejeon, 34141, Republic of Korea.

⁴Center for Multiscale Chiral Architectures (CMCA), KAIST, 291 Daehak-ro, Daejeon, 34141, Republic of Korea.

⁵Department of Convergence Medicine, Asan Medical Center, 88, Olympic-ro, Seoul, 05505, Republic of Korea.

⁶Department of Digital Medicine, College of Medicine, University of Ulsan, 88, Olympic-ro, Seoul, 05505, Republic of Korea.

D. Kim and C.-H. Whang contributed equally to this work.

CORRESPONDING AUTHORS : Hee-Seung Lee, Sangyong Jon

Abstract

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.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-18)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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