Targeting Delivery of Lidocaine and Cisplatin by Nanogel Enhances Chemotherapy and Alleviates Metastasis
Targeting Delivery of Lidocaine and Cisplatin by Nanogel Enhances Chemotherapy and Alleviates Metastasis
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纳米凝胶靶向输送利多卡因和顺铂可增强化疗并减轻转移
DOI：
10.1021/acsami.8b09376
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发表时间：
2018-08-01
影响因子：
9.5
通讯作者：
Yang, Qian
中科院分区：
文献类型：
--
作者：
Gao, Xiurong;Yang, Hui;Yang, Qian
抑制肿瘤生长、减少毒副作用、减轻肿瘤转移仍是肿瘤化疗需要克服的挑战。联合治疗为这些挑战提供了另一种解决方案。纳米粒因其多功能的载药能力和多功能的肿瘤靶向策略而成为联合治疗的理想载体。在这项研究中，cRGDfk修饰的纳米凝胶系统已被用来coload利多卡因，电压门控Na+通道抑制剂，和顺铂，一种常见的抗癌药物，以获得肿瘤靶向的双重药物负载纳米凝胶系统。利多卡因的引入不仅在体内外促进顺铂诱导的细胞凋亡，而且在小鼠模型中抑制了MDA-MB-231乳腺癌细胞的转移。此外，顺铂引起的体重减轻也得到了缓解，并且可以达到更高的剂量和更少的体重减轻，这表明顺铂介导的化疗引起的不良反应得到了缓解。此外，引入肽段-cRGDfk（其对α（v）β（3）整联蛋白具有高亲和力）进一步增加了肿瘤部位中载药纳米凝胶的富集。它有利于原发性肿瘤生长抑制。结果表明，通过配体修饰的纳米凝胶共载利多卡因和顺铂是α（v）β（3）整合素过表达乳腺癌联合治疗的一种有前途的策略。
Tumor growth inhibition and adverse effect reduction together with metastasis alleviation are still the challenges that need to be overcome in cancer chemotherapy. Combinational therapy provides an alternative solution for these challenges. Nanoparticles are the ideal carriers for combinational therapy due to their versatile drug loading capacities and versatile tumor-targeting strategies. In this study, a cRGDfk modified nanogel system has been utilized to coload lidocaine, a voltage-gated Na+ channels inhibitor, and cisplatin, a common anticancer drug to obtain a tumor-targeted dual drugs-loaded nanogel system. The introduction of lidocaine not only promotes the cisplatin-induced apoptosis in vitro and in vivo but also alleviates the metastasis of MDA-MB-231 breast cancer cells in the mouse model. Besides, the body weight loss caused by cisplatin has also been relieved, and higher dose with less body weight loss can be achieved, which indicated the adverse effect caused by cisplatin-mediated chemotherapy has been alleviated. Furthermore, the introduction of peptide segment-cRGDfk, which presents high affinity to alpha(v)beta(3) integrin, further increases the enrichment of drug-loaded nanogel in the tumor site. It favors the primary tumor growth inhibition. The results demonstrate the coloading of lidocaine and cisplatin by ligand-modified nanogels is a promising strategy for alpha(v)beta(3) integrin-overexpressing breast cancer combinational therapy.