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使用纳米载体将1型糖尿病治疗药物主动靶向胰腺β细胞。

Active targeting of type 1 diabetes therapies to pancreatic beta cells using nanocarriers.

作者信息

Collins Jillian, Farnsworth Nikki L

机构信息

Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO, USA.

出版信息

Diabetologia. 2025 Apr;68(4):692-703. doi: 10.1007/s00125-024-06356-5. Epub 2025 Jan 23.

Abstract

Type 1 diabetes is an autoimmune disease characterised by the destruction of pancreatic beta cells, resulting in lifelong insulin dependence. Although exogenous insulin can maintain glycaemic control, this approach does not protect residual or replacement pancreatic beta cells from immune-mediated death. Current therapeutics designed to protect functional beta cell mass or promote beta cell proliferation and regeneration can have off-target effects, resulting in higher dose requirements and adverse side effects. Targeted drug delivery using nanocarriers has demonstrated potential for overcoming these limitations. The critical bottleneck limiting the development of beta cell-targeted therapies is a lack of highly specific beta cell markers. This review provides an overview of the use of nanocarriers for cell-targeted delivery and the current state of the field of beta cell targeting. Technologies such as systematic evolution of ligands by exponential enrichment (SELEX) aptamer selection, phage display screening, and omics datasets from human samples are highlighted as tools to identify novel beta cell-specific targets that can be combined with nanocarriers for targeted delivery of therapeutics. Ultimately, beta cell-targeted therapies using nanocarriers present a unique opportunity to develop tailored treatments for each stage of type 1 diabetes with the goal of providing individuals with treatment options that prevent further progression or reverse the course of the disease.

摘要

1型糖尿病是一种自身免疫性疾病,其特征是胰腺β细胞被破坏,导致终身依赖胰岛素。尽管外源性胰岛素可以维持血糖控制,但这种方法并不能保护残余或替代的胰腺β细胞免受免疫介导的死亡。目前旨在保护功能性β细胞数量或促进β细胞增殖和再生的治疗方法可能会产生脱靶效应,导致更高的剂量需求和不良副作用。使用纳米载体进行靶向药物递送已显示出克服这些局限性的潜力。限制β细胞靶向治疗发展的关键瓶颈是缺乏高度特异性的β细胞标志物。本文综述了纳米载体在细胞靶向递送中的应用以及β细胞靶向领域的现状。通过指数富集的配体系统进化(SELEX)适体选择、噬菌体展示筛选和来自人类样本的组学数据集等技术被强调为识别新型β细胞特异性靶点的工具,这些靶点可与纳米载体结合用于治疗药物的靶向递送。最终,使用纳米载体的β细胞靶向治疗为1型糖尿病的每个阶段开发量身定制的治疗方法提供了独特的机会,目标是为个体提供预防疾病进一步进展或逆转病程的治疗选择。

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