2021-10-28

本期文章：《德国应用化学》：Online/在线发表

美国加州大学Liangfang Zhang团队提出了用于mRNA的细胞质传递的病毒模拟细胞膜涂层纳米颗粒。相关研究成果于2021年10月25日发表在《德国应用化学》。

细胞摄取后有效的内体逃逸是纳米给药领域的一个重大挑战，因为大多数药物有效载荷必须定位于亚细胞隔室而不是内体以发挥活性。在自然界中，病毒通过内吞后触发膜融合，很容易将其遗传物质传递到宿主细胞的细胞质中。对于甲型流感病毒，在其表面发现的血凝素（HA）蛋白在内体pH值下将病毒包膜与周围膜融合。

该文中，研究人员利用从表面表达HA的细胞中提取的膜涂层，制备了能够内体逃逸的仿生纳米颗粒。当在体外进行评估时，这些模拟病毒的纳米颗粒能够将mRNA有效载荷传递到靶细胞的细胞质区，从而成功表达编码的蛋白质。在体内给药时，在局部和全身给药方案中蛋白质表达水平显著增加。因此，利用基因工程方法在细胞膜包裹的纳米颗粒表面表达病毒融合蛋白是一种可行的策略，可用于调节包裹货物的细胞内定位。

附：英文原文

Title: Virus-Mimicking Cell Membrane-Coated Nanoparticles for Cytosolic Delivery of mRNA

Author: Joon Ho Park, Animesh Mohapatra, Jiarong Zhou, Maya Holay, Nishta Krishnan, Weiwei Gao, Ronnie H. Fang, Liangfang Zhang

Issue&Volume: 2021-10-25

Abstract: Effective endosomal escape after cellular uptake represents a major challenge in the field of nanodelivery, as the majority of drug payloads must localize to subcellular compartments other than the endosomes in order to exert activity. In nature, viruses can readily deliver their genetic material to the cytosol of host cells by triggering membrane fusion after endocytosis. For the influenza A virus, the hemagglutinin (HA) protein found on its surface fuses the viral envelope with surrounding membrane at endosomal pH values. Here, biomimetic nanoparticles capable of endosomal escape were fabricated using a membrane coating derived from cells engineered to express HA on their surface. When evaluated in vitro, these virus-mimicking nanoparticles were able to deliver an mRNA payload to the cytosolic compartment of target cells, resulting in the successful expression of the encoded protein. When the mRNA-loaded nanoparticles were administered in vivo, protein expression levels were significantly increased in both local and systemic delivery scenarios. We therefore conclude that utilizing genetic engineering approaches to express viral fusion proteins on the surface of cell membrane-coated nanoparticles is a viable strategy for modulating the intracellular localization of encapsulated cargoes.

DOI: 10.1002/anie.202113671

期刊信息

Angewandte Chemie：《德国应用化学》，创刊于1887年。隶属于德国化学会，最新IF：12.959