Targeted Nanoparticle‐Mediated Gene Therapy Mimics Oncolytic Virus for Effective Melanoma Treatment
Targeted Nanoparticle‐Mediated Gene Therapy Mimics Oncolytic Virus for Effective Melanoma Treatment
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DOI：
10.1002/adfm.201800173
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发表时间：
2018-05
影响因子：
19
通讯作者：
Li Luo;Yuping Yang;Ting Du;Tianyi Kang;Meimei Xiong;Hao Cheng;Yu Liu;Yujiao Wu;Yang Li;Yuwen Chen;Qianqian Zhang;Xuan Liu;Xiawei Wei;P. Mi;Zhigang She;G. Gao;Yuquan Wei;M. Gou
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文献类型：
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作者：
Li Luo;Yuping Yang;Ting Du;Tianyi Kang;Meimei Xiong;Hao Cheng;Yu Liu;Yujiao Wu;Yang Li;Yuwen Chen;Qianqian Zhang;Xuan Liu;Xiawei Wei;P. Mi;Zhigang She;G. Gao;Yuquan Wei;M. Gou
溶瘤病毒在肿瘤治疗中具有潜在的应用价值。然而，其临床应用受到病毒相关生物安全性问题的限制。在这里，受水泡性口炎病毒基质蛋白（VSVMP）在溶瘤性水泡性口炎病毒（VSV）诱导的细胞凋亡中的关键作用的启发，靶向纳米颗粒递送的中性VSVMP基因制剂被设计成像VSV一样用于癌症治疗。该VSVMP制剂由CRGDKGPDC肽修饰的杂合单甲氧基聚乙二醇-聚丙交酯纳米颗粒与VSVMP质粒复合而成，具有良好的血液相容性和肿瘤靶向能力。转染效率与VSV相当。静脉给药后，VSVMP制剂能有效靶向肿瘤，显著抑制黑色素瘤生长和转移，延长荷瘤小鼠的生存时间，且无明显全身毒性。其抗肿瘤机制包括诱导细胞凋亡、抑制血管生成和激活一些病毒相关信号通路。这项工作证明了VSV启发的非病毒基因疗法在黑色素瘤治疗中具有很好的临床应用前景。
Oncolytic virus has potential applications in cancer therapy. However, its clinical application is restricted by the virus‐associated biosafety issues. Here, inspired by the key role of vesicular stomatitis virus matrix protein (VSVMP) in the oncolytic vesicular stomatitis virus (VSV) induced apoptosis, a targeted nanoparticle‐delivered neutral VSVMP gene formulation is designed to act like the VSV for cancer therapy. This VSVMP formulation consists of a CRGDKGPDC peptide modified hybrid monomethoxy poly (ethylene glycol)‐poly(d,l‐lactide) nanoparticles complexed with VSVMP plasmid, having good blood compatibility and tumor targeting ability. The transfection efficiency is as high as that of VSV. After intravenous administration, the VSVMP formulation can efficiently target the tumor, significantly inhibit the melanoma growth and metastasis, prolong the survival time of tumor‐bearing mice, and does not cause obvious systemic toxicity. The anticancer mechanisms involve apoptosis induction, angiogenesis inhibition and some virus‐associated signal pathways activation. This work demonstrates a VSV‐inspired nonviral gene therapy that has promising clinical applications in melanoma treatment.