Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology , Wuhan, Hubei 430022, P. R. China.
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education , 826 Zhangheng Road, Shanghai 201203, P. R. China.
ACS Appl Mater Interfaces. 2017 Sep 20;9(37):31497-31508. doi: 10.1021/acsami.7b09458. Epub 2017 Sep 8.
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.
由于富含基质和血液灌注不良，胰腺导管腺癌（PDA）是一种难以通过化疗药物有效治疗的恶性肿瘤。许多综述广泛提倡通过肿瘤微环境调节或先进的纳米医学设计来实现更好的治疗效果，以治疗 PDA。在本研究中，通过肿瘤微环境调节和先进的仿生金纳米棒设计相结合，开发了一种新的 PDA 光热治疗策略。一方面，通过将金纳米棒（GNRs）包裹在红细胞膜上来制备仿生金纳米棒（MGNRs）。结果表明，MGNRs 在体外具有更高的胶体稳定性、更强的光热治疗效果和更长的体内循环时间。另一方面，环巴胺处理可成功破坏 PDA 的细胞外基质，改善肿瘤血液灌注。此外，环巴胺处理使 MGNRs 在肿瘤中的积累增加了 1.8 倍，因此在体内产生了比对照组更高的光热效率。最后，环巴胺处理联合光热 MGNRs 使 Capan-2 肿瘤异种移植物的收缩最为显著。因此，通过肿瘤微环境调节和长循环仿生 MGNRs 的综合优势，实现了对 PDA 的有效光热治疗。总的来说，这种结合肿瘤微环境调节和先进仿生纳米粒子设计的新策略在 PDA 治疗中可能具有巨大的潜力。
