Huang Shengnan, Li Chunming, Wang Weiping, Li Huanjie, Sun Zhi, Song Chengzhi, Li Benyi, Duan Shaofeng, Hu Yurong
Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People's Republic of China.
Department of Pharmacy, Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing, People's Republic of China.
Int J Nanomedicine. 2017 Jul 20;12:5163-5176. doi: 10.2147/IJN.S131089. eCollection 2017.
The combination of photothermal therapy and chemotherapy (photothermal-chemotherapy) is a promising strategy for cancer therapy. Gold nanocages (AuNCs), with hollow and porous structures and unique optical properties, have become a rising star in the field of drug delivery. Here, we designed a novel targeted drug delivery system based on functionalized AuNCs and evaluated their therapeutic effects in vitro and in vivo. We then loaded doxorubicin into this promising system, designated as DHTPAuNCs consisting of hyaluronic acid-grafted and A54 peptide-targeted PEGylated AuNCs. Its formation was corroborated by ultraviolet-visible spectroscopy, transmission electron microscopy and dynamic light scattering. This delivery platform needed hyaluronidase to release encapsulated drugs, meanwhile the acidic pH and near-infrared irradiation could accelerate the release. In addition, the results of cellular uptake demonstrate that this system could bind specifically with BEL-7402 cells. In vitro, we evaluated therapeutic effects of the DHTPAuNCs in BEL-7402 cells by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay. Moreover, in BEL-7402 tumor-bearing nude mice, its therapy effect in vivo was also evaluated. As expected, DHTPAuNCs exhibited excellent therapeutic effect by photothermal-chemotherapy, both in vitro and in vivo. In short, DHTPAuNCs with low toxicity showed great potential as a drug delivery system for cancer therapy.
光热疗法与化疗相结合（光热化疗）是一种很有前景的癌症治疗策略。具有中空多孔结构和独特光学性质的金纳米笼（AuNCs）已成为药物递送领域的一颗新星。在此，我们设计了一种基于功能化金纳米笼的新型靶向药物递送系统，并评估了其在体外和体内的治疗效果。然后我们将阿霉素加载到这个有前景的系统中，该系统被命名为DHTPAuNCs，由透明质酸接枝且A54肽靶向的聚乙二醇化金纳米笼组成。通过紫外可见光谱、透射电子显微镜和动态光散射证实了其形成。该递送平台需要透明质酸酶来释放封装的药物，同时酸性pH值和近红外照射可加速释放。此外，细胞摄取结果表明该系统可与BEL - 7402细胞特异性结合。在体外，我们通过3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐法评估了DHTPAuNCs对BEL - 7402细胞的治疗效果。此外，在荷BEL - 7402肿瘤的裸鼠中，还评估了其体内治疗效果。正如预期的那样，DHTPAuNCs通过光热化疗在体外和体内均表现出优异的治疗效果。简而言之，低毒性的DHTPAuNCs作为癌症治疗的药物递送系统具有巨大潜力。
