Cell membrane (CM) coating technology is increasingly being applied in nanomedicine, but the entire coating procedure including adsorption, rupture, and fusion is not completely understood. Previously, we showed that the majority of biomimetic nanoparticles (NPs) were only partially coated, but the mechanism underlying this partial coating remains unclear, which hinders the further improvement of the coating technique. Here, we show that partial coating is an intermediate state due to the adsorption of CM fragments or CM vesicles, the latter of which could eventually be ruptured under external force. Such partial coating is difficult to self-repair to achieve full coating due to the limited membrane fluidity. Building on our understanding of the detailed coating process, we develop a general approach for fixing the partial CM coating: external phospholipid is introduced as a helper to increase CM fluidity, promoting the final fusion of lipid patches. The NPs coated with this approach have a high ratio of full coating (~23%) and exhibit enhanced tumor targeting ability in comparison to the NPs coated traditionally (full coating ratio of ~6%). Our results provide a mechanistic basis for fixing partial CM coating towards enhancing tumor accumulation.

细胞膜 (CM) 涂层技术越来越多地应用于纳米医学，但包括吸附、破裂和融合在内的整个涂层过程尚不完全清楚。此前，我们发现大多数仿生纳米粒子 (NPs) 仅被部分包覆，但这种部分包覆的机制仍不清楚，这阻碍了包覆技术的进一步改进。在这里，我们表明由于 CM 碎片或 CM 囊泡的吸附，部分涂层是一种中间状态，后者最终可能在外力作用下破裂。由于膜的流动性有限，这种部分包覆很难自我修复以实现全包覆。基于我们对详细涂层过程的理解，我们开发了一种修复部分 CM 涂层的通用方法：引入外部磷脂作为辅助剂以增加 CM 流动性，促进脂质块的最终融合。用这种方法包被的 NPs 具有很高的全包被率 (~23%)，与传统包被的 NPs（全包被率约为 6%）相比，表现出增强的肿瘤靶向能力。我们的结果为固定部分 CM 涂层以增强肿瘤积累提供了机制基础。