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Tobacco mosaic virus delivery of mitoxantrone for cancer therapy
Nanoscale ( IF 5.8 ) Pub Date : 2018-08-21 00:00:00 , DOI: 10.1039/c8nr04142c
Richard D. Lin 1, 2, 3, 4 , Nicole F. Steinmetz 1, 2, 3, 4, 5
Affiliation  

Mitoxantrone (MTO) is a topoisomerase II inhibitor which has been used to treat various forms of cancer either as a solo chemotherapy regimen or as a component in cocktail treatments. However, as with other anti-neoplastic agents, MTO has severe cardiac side effects. Therefore, a drug delivery approach holds promise to improve the safety and applicability of this chemotherapy. Here, we report the application of a plant virus-based nanotechnology derived from tobacco mosaic virus (TMV) as a delivery vehicle for MTO towards cancer therapy. TMV is a high aspect-ratio, soft-matter nanotube with dimensions of 300 × 18 nm and a 4 nm wide channel. The surface chemistry of the interior and exterior TMV surfaces is distinct and we established charge-driven drug loading strategies to encapsulate therapeutics for drug delivery. We demonstrate effective MTO loading into TMV yielding ∼1000 MTO per TMV carrier. The treatment efficacy of MTO-loaded TMV (MTOTMV) was assessed in in vitro and in vivo models. In vitro testing confirmed that MTO maintained its efficacy when delivered by TMV in a panel of cancer cell lines. Drug delivery in vivo using a mouse model of triple negative breast cancer demonstrated the superior efficacy of TMV-delivered MTO vs. free MTO. This study demonstrates the potential of plant virus-based nanotechnology for cancer therapy and drug delivery.

中文翻译:

烟草花叶病毒传递米托蒽醌用于癌症治疗

米托蒽醌(MTO)是一种拓扑异构酶II抑制剂,已被用作单独的化疗方案或鸡尾酒疗法的组成部分来治疗各种形式的癌症。但是,与其他抗肿瘤药一样,MTO具有严重的心脏副作用。因此,药物递送方法有望改善该化学疗法的安全性和适用性。在这里,我们报道了基于烟草花叶病毒(TMV)的基于植物病毒的纳米技术作为MTO向癌症治疗的传递载体的应用。TMV是高纵横比的软物质纳米管,尺寸为300×18 nm,通道宽度为4 nm。TMV内表面和外表面的表面化学性质截然不同,我们建立了电荷驱动的载药策略来封装用于药物递送的治疗剂。我们证明了有效的MTO加载到TMV中,每个TMV载波产生约1000 MTO。载有MTO的TMV(在体外体内模型中评估了MTO TMV)。体外测试证实,当通过TMV在一组癌细胞系中传递MTO时,MTO保持了其功效。使用三阴性乳腺癌小鼠模型的体内药物递送证明了TMV递送的MTO游离MTO相比具有更高的功效。这项研究证明了基于植物病毒的纳米技术在癌症治疗和药物输送中的潜力。
更新日期:2018-08-21
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