Institute of Optoelectronics, Fudan University, Shanghai, 200433, China.
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, 4072, Australia.
Nat Commun. 2024 Feb 29;15(1):1891. doi: 10.1038/s41467-024-46189-9.
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.
细胞膜裂解是一种有效的抗癌策略，主要依赖于可溶性分子膜溶剂。然而，基于纳米材料的膜溶剂在很大程度上尚未得到探索。在此，我们通过纳米级和分子级的多图案化策略引入了介孔膜溶纳米穿孔剂 (MLNPs)，其具有刺状表面形貌（纳米级图案化）和刺上苯桥有机硅组成的分子级周期性（分子级图案化），协同赋予内在的膜溶活性。计算模型揭示了纳米刺介导的多价穿孔行为，即与单个刺相比，多个刺诱导非直线扩大的膜孔，并且苯基团与磷脂分子平行排列显示出比其他排列更高的结合能，这支持了分子有序性在磷脂提取中对膜溶作用的重要性。最后，在雌性 Balb/c 小鼠模型中证明了 MLNPs 的抗肿瘤活性。这项工作展示了基于有机硅的生物活性纳米结构的组装，使我们能够对纳米/分子模式共同控制的纳米-生物相互作用有新的理解。
