Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles

Lizhi Liu, Xuan Bai, Maria-Viola Martikainen, Anna Kårlund, Marjut Roponen, Wujun Xu (), Guoqing Hu, Ennio Tasciotti and Vesa-Pekka Lehto ()
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Lizhi Liu: University of Eastern Finland
Xuan Bai: State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University
Maria-Viola Martikainen: University of Eastern Finland
Anna Kårlund: Institute of Public Health and Clinical Nutrition, University of Eastern Finland
Marjut Roponen: University of Eastern Finland
Wujun Xu: University of Eastern Finland
Guoqing Hu: State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University
Ennio Tasciotti: IRCCS San Raffaele Pisana Hospital and San Raffaele University
Vesa-Pekka Lehto: University of Eastern Finland

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Cell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (

Date: 2021
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DOI: 10.1038/s41467-021-26052-x

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