Systematic design of cell membrane coating to improve tumor targeting of nanoparticles

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 (similar to 23%) and exhibit enhanced tumor targeting ability in comparison to the NPs coated traditionally (full coating ratio of similar to 6%). Our results provide a mechanistic basis for fixing partial CM coating towards enhancing tumor accumulation.

Automated summary

The mechanism underlying partial coating in cell membrane (CM) coating technology has been revealed to be the adsorption of CM fragments or vesicles, which can eventually be ruptured under external force. Partial coating is difficult to self-repair due to limited membrane fluidity. Introducing external phospholipids as a helper can increase CM fluidity and promote the final fusion of lipid patches.