Virion‐Like Membrane‐Breaking Nanoparticles with Tumor‐Activated Cell‐and‐Tissue Dual‐Penetration Conquer Impermeable Cancer |
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| Authors: | Xiao Zhang Xianghui Xu Yachao Li Cheng Hu Zhijun Zhang Zhongwei Gu |
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| Affiliation: | 1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, P. R. China;2. College of Materials Science and Engineering, Nanjing Tech University, Nanjing, Jiangsu, P. R. China |
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| Abstract: | Poor drug penetration into tumor cells and tissues is a worldwide difficulty in cancer therapy. A strategy is developed for virion‐like membrane‐breaking nanoparticles (MBNs) to smoothly accomplish tumor‐activated cell‐and‐tissue dual‐penetration for surmounting impermeable drug‐resistant cancer. Tailor‐made dendritic arginine‐rich peptide prodrugs are designed to mimic viral protein transduction domains and globular protein architectures. Attractively, these protein mimics self‐assemble into virion‐like nanoparticles in aqueous solution, having highly ordered secondary structure. Tumor‐specific acidity conditions would activate the membrane‐breaking ability of these virion‐like nanoparticles to perforate artificial and natural membrane systems. As expected, MBNs achieve highly efficient drug penetration into drug‐resistant human ovarian (SKOV3/R) cancer cells. Most importantly, the well‐organized MBNs can pass through endothelial/tumor cells and spread from one cell to another one. Intravenous injection of MBNs into nude mice bearing impermeable SKOV3/R tumors suggests that the MBNs can recognize the tumor tissue after prolonged blood circulation, evoke the membrane‐breaking function for robust transvascular extravasation, and penetrate into the deep tumor tissue. This work provides the first demonstration of sophisticated molecular and supramolecular engineering of virion‐like MBNs to realize the long‐awaited cell‐and‐tissue dual‐penetration, contributing to the development of a brand‐new avenue for dealing with incurable cancers. |
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| Keywords: | impermeable cancer membrane‐breaking capacity multidrug resistance reversal tumor penetration virion‐like nanoparticles |
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