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

Lizhi Liu, Dingyi Pan, Sheng Chen, Maria-Viola Martikainen, Anna Kårlund, Jing Ke, Herkko Pulkkinen, Hanna Ruhanen, Marjut Roponen, Reijo Käkelä, Wujun Xu (), Jie Wang () and Vesa-Pekka Lehto ()
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Lizhi Liu: University of Eastern Finland
Dingyi Pan: Zhejiang University
Sheng Chen: Yale University
Maria-Viola Martikainen: University of Eastern Finland
Anna Kårlund: University of Eastern Finland
Jing Ke: Boston College
Herkko Pulkkinen: University of Eastern Finland
Hanna Ruhanen: University of Helsinki
Marjut Roponen: University of Eastern Finland
Reijo Käkelä: University of Helsinki
Wujun Xu: University of Eastern Finland
Jie Wang: Anhui Medical University
Vesa-Pekka Lehto: University of Eastern Finland

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-33889-3

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