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

中文翻译：

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具有不同器官选择性的糖萼模拟纳米粒子用于药物输送和治疗

器官选择性药物输送有望最大限度地提高各种治疗方式的功效，同时最大限度地减少其全身毒性。脂质纳米粒子和聚合物囊泡可以指导 mRNA 或基因编辑机器的器官选择性递送，但它们的递送主要限于肝脏、脾脏和肺。我们迫切需要一个能够将药物输送到这些和其他目标器官的平台。在这里，我们生成了一个包含五个随机组合的糖部分的糖萼模拟纳米颗粒（GlyNP）文库，并使用直接体内文库筛选来识别在肝脏、脾脏、肺、肾脏、心脏和大脑中优先生物分布的 GlyNP。每个器官靶向 GlyNP 命中均显示器官内的细胞向性。肝脏、肾脏和脾脏靶向 GlyNP 命中搭配治疗剂可有效缓解小鼠中对乙酰氨基酚诱导的肝损伤、顺铂诱导的肾损伤和免疫性血小板减少症的症状。此外，GlyNP 命中的差异器官靶向不受蛋白质冠的影响，而是受其表面展示的糖部分的影响。我们设想，我们基于 GlyNP 的平台可以实现治疗药物的器官和细胞靶向递送。本文受版权保护。版权所有