Bioinspired Artificial Tobacco Mosaic Virus with Combined Oncolytic Properties to Completely Destroy Multidrug‐Resistant Cancer

• Published in: Advanced materials (Weinheim) 2020-03, Vol.32 (9), p.e1904958-n/a
• Main Authors: Wu, Huayu, Zhong, Dan, Zhang, Zhijun, Li, Yachao, Zhang, Xiao, Li, Yunkun, Zhang, Zhuangzhuang, Xu, Xianghui, Yang, Jun, Gu, Zhongwei
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; artificial tobacco mosaic virus; Biomimetic Materials - chemistry; biomimetic strategies; Biomimetics; Calcium ions; Cell Line, Tumor; Cell Membrane Permeability; Colon; Colonic Neoplasms - drug therapy; Construction; Delayed-Action Preparations - chemistry; Disruption; Doxorubicin - chemistry; Doxorubicin - therapeutic use; Drug Carriers - chemistry; Drug Liberation; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Drug Stability; Endoplasmic reticulum; Fluorescent Dyes - chemistry; Humans; Hydrazones - chemistry; Materials science; Mice, Nude; multidrug resistance reversal; Nanotubes, Carbon - chemistry; Oligopeptides - chemistry; oncolytic viruses; Optical Imaging; Optimization; Phototherapy; secondary infection; Shielding; Single wall carbon nanotubes; Structural stability; Surface Properties; Tissue Distribution; Tobacco; Tobacco Mosaic Virus - chemistry; Viruses
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.201904958

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, ≈500 mm3). Artificial tobacco mosaic virus (ATMV), which highly mimicks both the typical elongated structure and biobehavior of natural TMVs, is ingeniously endowed with robust oncolytic properties, achieving composite therapies to completely defeat large‐sized drug‐resistant colon tumors. This work provides broad possibilities for novel virus‐like strategies that optimize the morphological features of versatile oncolytic functions to address complicated cancer environments.