Tumor Microenvironment Modulation by Cyclopamine Improved Photothermal Therapy of Biomimetic Gold Nanorods for Pancreatic Ductal Adenocarcinomas
Tumor Microenvironment Modulation by Cyclopamine Improved Photothermal Therapy of Biomimetic Gold Nanorods for Pancreatic Ductal Adenocarcinomas
复制标题
环巴明调节肿瘤微环境改进仿生金纳米棒光热疗法治疗胰腺导管腺癌
DOI：
10.1021/acsami.7b09458
复制
发表时间：
2017-09-20
影响因子：
9.5
通讯作者：
Jiang, Xinguo
中科院分区：
文献类型：
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作者：
Jiang, Ting;Zhang, Bo;Jiang, Xinguo
胰腺导管腺癌（pancreatic ductal adenocarcinoma，PDA）由于间质丰富、血流灌注差，是一种难治性肿瘤，化疗药物难以有效治疗。肿瘤微环境调节或先进的纳米药物设计，以实现更好的治疗PDA治疗的好处是广泛提倡的许多评论。本研究将肿瘤微环境调控与仿生金纳米棒的先进设计相结合，提出了一种新的PDA光热治疗策略。一方面，将金纳米棒（GNRs）与红细胞膜（MGNRs）包覆在一起，形成仿生金纳米棒。结果表明，MGNRs的体外胶体稳定性、体外光热治疗效果和体内循环时间均显著高于GNRs。另一方面，通过环巴胺治疗的肿瘤微环境调节成功地破坏了PDA的细胞外基质并改善了肿瘤血液灌注。此外，环巴胺治疗显着增加了1.8倍的MGNRs在肿瘤中的积累，因此在体内产生更高的光热效率比对照组。最后，在所有治疗组中，环巴胺治疗与光热MGNR组合实现了Capan-2肿瘤异种移植物的最显著收缩。因此，利用肿瘤微环境调控和长循环仿生MGNRs的综合优势，实现了PDA的有效光热治疗。总之，这种结合肿瘤微环境调节和仿生纳米颗粒先进设计的新策略在PDA治疗中可能具有巨大的潜力。
Due to the rich stroma content and poor blood perfusion, pancreatic ductal adenocarcinoma (PDA) is a tough cancer that can hardly be effectively treated by chemotherapeutic drugs. Tumor microenvironment modulation or advanced design of nanomedicine to achieve better therapeutic benefits for PDA treatment was widely advocated by many reviews. In the present study, a new photothermal therapy strategy of PDA was developed by combination of tumor microenvironment modulation and advanced design of biomimetic gold nanorods. On one hand, biomimetic gold nanorods were developed by coating gold nanorods (GNRs) with erythrocyte membrane (MGNRs). It was shown that MGNRs exhibited significantly higher colloidal stability in vitro, stronger photothermal therapeutic efficacy in vitro, and longer circulation in vivo than GNRs. On the other hand, tumor microenvironment modulation by cyclopamine treatment successfully disrupted the extracellular matrix of PDA and improved tumor blood perfusion. Moreover, cyclopamine treatment significantly increased the accumulation of MGNRs in tumors by 1.8-fold and therefore produced higher photothermal efficiency in vivo than the control group. Finally, cyclopamine treatment combined with photothermal MGNRs achieved the most significant shrinkage of Capan-2 tumor xenografts among all the treatment groups. Therefore, with the integrated advantages of tumor microenvironment regulation and long-circulation biomimetic MGNRs, effective photothermal therapy of PDA was achieved. In general, this new strategy of combining tumor microenvironment modulation and advanced design of biomimetic nanoparticles might have great potential in PDA therapy.