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 ).

中文翻译：

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具有结合溶瘤特性的生物启发式人工烟草花叶病毒，可完全消灭耐多药癌症。

尽管仿生病毒样策略已广泛用于抗肿瘤应用中，但独特形状的病毒样剂的构建和优化其特定形态特征以实现多种抗肿瘤功能仍然是值得追求的目标。在这里，开发了一种新的策略来构建紧密模仿杆状烟草花叶病毒（TMV）结构的人工烟草花叶病毒（ATMV）。超分子阵列是从特制的衣壳模拟树突的小的，重复的亚基中自动组装到RGD修饰的单壁碳纳米管上的，以构建具有高结构稳定性的ATMV。ATMV的设计巧妙地采用了屏蔽，靶向和布防方法，包括屏蔽病毒以防过早消除，选择性地靶向肿瘤组织，并以溶瘤能力武装病毒。细长的颗粒被隐藏在血液中，直到它们到达肿瘤部位，然后它们诱导强大的复合溶瘤过程，包括细胞膜渗透，内质网破坏以引起Ca 2+释放，化学疗法递送和光热疗法。令人兴奋的是，ATMV不仅裂解原发感染的细胞，而且渗透到相邻细胞中进行继发感染，使细胞间扩散，甚至在实体瘤深处继续诱导裂解。这项工作激发了具有独特优化形状的溶瘤功能的独特形状的病毒样药物，该药物完全击败了大型耐药结肠癌（LoVo / Adr，≈500mm3）。然后，它们诱导了强大的复合溶瘤过程，包括细胞膜渗透，内质网破坏以引起Ca2 +释放，化学疗法递送和光热疗法。令人兴奋的是，ATMV不仅裂解原发感染的细胞，而且渗透到相邻细胞中进行继发感染，使细胞间扩散，甚至在实体瘤深处继续诱导裂解。这项工作激发了具有独特优化形状的溶瘤功能的独特形状的病毒样药物，该药物完全击败了大型耐药结肠癌（LoVo / Adr，≈500mm3）。然后，它们诱导了强大的复合溶瘤过程，包括细胞膜渗透，内质网破坏以引起Ca2 +释放，化学疗法递送和光热疗法。令人兴奋的是，ATMV不仅裂解原发感染的细胞，而且渗透到相邻细胞中进行继发感染，使细胞间扩散，甚至在实体瘤深处继续诱导裂解。这项工作激发了具有独特优化形状的溶瘤功能的独特形状的病毒样药物，该药物完全击败了大型耐药结肠癌（LoVo / Adr，≈500mm3）。在实体瘤之间扩散，并持续诱导裂解，甚至深入实体瘤。这项工作激发了具有独特优化形状的溶瘤功能的独特形状的病毒样药物，该药物完全击败了大型耐药结肠癌（LoVo / Adr，≈500mm3）。在实体瘤中扩散到细胞之间并继续诱导裂解。这项工作激发了具有独特优化形状的溶瘤功能的独特形状的病毒样药物，该药物完全击败了大型耐药结肠癌（LoVo / Adr，≈500mm3）。