期刊
ADVANCED MATERIALS
卷 32, 期 9, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201904958
关键词
artificial tobacco mosaic virus; biomimetic strategies; multidrug resistance reversal; oncolytic viruses; secondary infection
类别
资金
- National Natural Science Foundation of China [81621003, 21674067, 31771067]
- National Key Research and Development Program of China [2017YFC1103501]
- Key R&D Plan of Jiangsu Province [BE2018010-3]
- Scientific Research Foundation for Talent Introduction of Nanjing Tech University [39803130, 39803134]
Although biomimetic virus-like strategies have been widely used in antitumor applications, construction of uniquely shaped virus-like agents and optimization of their specific morphological features to achieve diverse antitumor functions are worthwhile pursuits. Here, a novel strategy to construct an artificial tobacco mosaic virus (ATMV) that closely mimics the structure of the rod-like tobacco mosaic virus (TMV) is developed. The supramolecular array is self-assembled from small, repeated subunits of tailor-made capsid-mimicking dendrons onto RGD-modified single-walled carbon nanotube to construct the ATMVs with high structural stability. The ATMVs are tactfully designed with shielding, targeting, and arming approaches, including shielding the viruses against premature elimination, selectively targeting tumor tissue, and arming the viruses with oncolytic abilities. The elongated particles are concealed in blood until they arrived at a tumor site, then they induce robust composite oncolytic processes including cytomembrane penetration, endoplasmic reticulum disruption to cause Ca2+ release, chemotherapeutic delivery, and photothermal therapy. Excitingly, the ATMVs not only lyse primary infected cells, but permeate adjacent cells for secondary infection, spreading cell-to-cell and continuing to induce lysis even deep in solid tumors. This work inspires a uniquely shaped virus-like agent with tactically optimized oncolytic functions that completely defeated large drug-resistant colon tumor (LoVo/Adr, approximate to 500 mm(3)).
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