Mesoporous nanoperforators as membranolytic agents via nano- and molecular-scale multi-patterning

Yannan Yang (), Shiwei Chen, Min Zhang (), Yiru Shi, Jiangqi Luo, Yiming Huang, Zhengying Gu, Wenli Hu, Ye Zhang, Xiao He () and Chengzhong Yu ()
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Yannan Yang: Fudan University
Shiwei Chen: East China Normal University
Min Zhang: Tongji University School of Medicine
Yiru Shi: The University of Queensland
Jiangqi Luo: The University of Queensland
Yiming Huang: Tongji University School of Medicine
Zhengying Gu: East China Normal University
Wenli Hu: East China Normal University
Ye Zhang: East China Normal University
Xiao He: East China Normal University
Chengzhong Yu: The University of Queensland

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Plasma membrane lysis is an effective anticancer strategy, which mostly relying on soluble molecular membranolytic agents. However, nanomaterial-based membranolytic agents has been largely unexplored. Herein, we introduce a mesoporous membranolytic nanoperforators (MLNPs) via a nano- and molecular-scale multi-patterning strategy, featuring a spiky surface topography (nanoscale patterning) and molecular-level periodicity in the spikes with a benzene-bridged organosilica composition (molecular-scale patterning), which cooperatively endow an intrinsic membranolytic activity. Computational modelling reveals a nanospike-mediated multivalent perforation behaviour, i.e., multiple spikes induce nonlinearly enlarged membrane pores compared to a single spike, and that benzene groups aligned parallelly to a phospholipid molecule show considerably higher binding energy than other alignments, underpinning the importance of molecular ordering in phospholipid extraction for membranolysis. Finally, the antitumour activity of MLNPs is demonstrated in female Balb/c mouse models. This work demonstrates assembly of organosilica based bioactive nanostructures, enabling new understandings on nano-/molecular patterns co-governed nano-bio interaction.

Date: 2024
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DOI: 10.1038/s41467-024-46189-9

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