Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan, Republic of China,
Research Center of Applied Sciences (RCAS), Academia Sinica, Taipei, 11529, Taiwan, Republic of China.
Int J Nanomedicine. 2018 Dec 21;14:181-193. doi: 10.2147/IJN.S177851. eCollection 2019.
A biocompatible nanocomplex system co-encapsulated with gold nanorods (AuNRs) and doxorubicin (DOX) was investigated for its potentials on the combined photothermal- and chemotherapy.
Hydrophobic AuNRs were synthesized by the hexadecyltrimethyl-ammonium bromide (CTAB)-mediated seed growth method, and then, they received two-step surface modifications of polyethylene glycol (PEG) and dodecane. The AuNR/DOX/poly(lactic--glycolic acid) (PLGA) nanocomplexes were prepared by emulsifying DOX, AuNR, and PLGA into aqueous polyvinyl alcohol solution by sonication. Human serum albumin (HSA) was used to coat the nanocomplexes to afford HSA/AuNR/DOX-PLGA (HADP). Size and surface potential of the HADP nanocomplexes were determined by using a Zetasizer. Cytotoxicity and cellular uptake of the HADP were analyzed by using MTT assay and flow cytometry, respectively. In vitro anticancer effects of the HADP were studied on various cancer cell lines. To assess the therapeutic efficacy, CT26 tumor-bearing mice were intravenously administered with HADP nanocomplexes and laser treatments, followed by monitoring of the tumor growth and body weight.
Size and surface potential of the HADP nanocomplexes were 245.8 nm and -8.6 mV, respectively. Strong photothermal effects were verified on the AuNR-loaded PLGA nanoparticles (NPs) in vitro. Rapid and repeated drug release from the HADP nanocomplexes was successfully achieved by near-infrared (NIR) irradiations. HSA significantly promoted cellular uptake of the HADP nanocomplexes to murine colon cancer cells as demonstrated by cell imaging and flow cytometric studies. By combining photothermal and chemotherapy, the HADP nanocomplexes exhibited strong synergistic anticancer effects in vitro and in vivo.
An NIR-triggered drug release system by encapsulating hydrophobic AuNR and DOX inside the PLGA NPs has been successfully prepared in this study. The HADP NPs show promising combined photothermal- and chemotherapeutic effects without inducing undesired side effects on a murine colon cancer animal model.
研究共包载金纳米棒（AuNRs）和阿霉素（DOX）的生物相容性纳米复合物系统在光热-化学联合治疗中的潜力。
通过十六烷基三甲基溴化铵（CTAB）介导的种子生长法合成疏水性 AuNRs，然后通过两步法进行聚乙二醇（PEG）和十二烷的表面修饰。通过超声将 DOX、AuNR 和聚乳酸-羟基乙酸共聚物（PLGA）乳化到水性聚乙烯醇溶液中，制备 AuNR/DOX/聚（乳酸-羟基乙酸）（PLGA）纳米复合物。人血清白蛋白（HSA）用于包覆纳米复合物，得到 HSA/AuNR/DOX-PLGA（HADP）。使用 Zetasizer 测定 HADP 纳米复合物的粒径和表面电位。通过 MTT 法和流式细胞术分别分析 HADP 的细胞毒性和细胞摄取。在各种癌细胞系上研究了 HADP 的体外抗癌作用。为了评估治疗效果，将 CT26 荷瘤小鼠静脉给予 HADP 纳米复合物和激光治疗，然后监测肿瘤生长和体重。
HADP 纳米复合物的粒径和表面电位分别为 245.8nm 和-8.6mV。体外证实了负载 AuNR 的 PLGA 纳米颗粒（NPs）具有很强的光热效应。通过近红外（NIR）照射，成功地实现了 HADP 纳米复合物的快速、重复药物释放。细胞成像和流式细胞术研究表明，HSA 显著促进了 HADP 纳米复合物向鼠结肠癌细胞的摄取。通过光热和化疗相结合，HADP 纳米复合物在体外和体内均表现出强烈的协同抗癌作用。
本研究成功制备了一种包封疏水性 AuNR 和 DOX 在内的 PLGA NPs 的 NIR 触发药物释放系统。HADP 纳米颗粒在鼠结肠癌动物模型中表现出有前景的光热-化学联合治疗效果，且没有引起不良的副作用。
