近日，美国加州大学圣地亚哥分校Liangfang Zhang团队实现了通过点击化学控制细胞纳米片的二聚化以增强免疫相容性。2025年8月10日出版的《美国化学会志》发表了这项最新研究成果。

细胞纳米盘（CNDs）由细胞膜碎片组装并用支架分子稳定，已成为一种有前途的药物递送、对策和疫苗接种的仿生平台。然而，暴露于当前CND结构中的内膜成分，如磷脂酰丝氨酸（PS），可触发免疫识别和快速清除，从而限制了其治疗效果。

为了解决这一问题，研究组报道了一种独特的方法，通过点击化学将两个单体CNDs共价连接，以精确控制的方式使CNDs二聚化，旨在屏蔽免疫原性内膜成分。与单体CNDs相比，二聚体CNDs显示PS暴露减少，巨噬细胞摄取减少，体内循环延长。在急性肺损伤和全身性炎症模型中，二聚体CNDs具有优异的细胞因子抑制和良好的生物分布，且短期毒性最小。这些发现表明，CND二聚化可以有效增强免疫相容性，大大提高体内性能，提高了细胞膜源性CND技术的应用潜力。

附：英文原文

Title: Controlled Dimerization of Cellular Nanodiscs via Click Chemistry to Enhance Immune Compatibility

Author: Lei Sun, Yiyan Yu, Jiayuan Alex Zhang, Wei-Ting Shen, Kailin Feng, Dean Bai, Zhidong Zhou, Weiwei Gao, Liangfang Zhang

Issue&Volume: August 10, 2025

Abstract: Cellular nanodiscs (CNDs), assembled from cell membrane fragments and stabilized with scaffold molecules, have emerged as a promising biomimetic platform for drug delivery, countermeasures, and vaccination. However, the exposure of inner membrane components in the current CND constructs, such as phosphatidylserine (PS) can trigger immune recognition and rapid clearance, thereby limiting their therapeutic efficacy. To address this issue, here we report on a unique approach to dimerizing CNDs in a precisely controlled, back-to-back manner by covalently linking two monomeric CNDs via click chemistry, aiming to shield the immunogenic inner membrane components. Compared with monomeric CNDs, the resulting dimeric CNDs showed reduced PS exposure, decreased macrophage uptake, and prolonged circulation in vivo. In mouse models of acute lung injury and systemic inflammation, dimeric CNDs achieved superior cytokine suppression and favorable biodistribution with minimal short-term toxicity. These findings demonstrate that CND dimerization can effectively enhance immune compatibility and greatly improve in vivo performance, advancing the application potential of cell membrane-derived CND technology.

DOI: 10.1021/jacs.5c07920

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c07920