Hepatocellular Carcinoma: Intra-arterial Delivery of Doxorubicin-loaded Hollow Gold Nanospheres for Photothermal Ablation-Chemoembolization Therapy in Rats.
Hepatocellular Carcinoma: Intra-arterial Delivery of Doxorubicin-loaded Hollow Gold Nanospheres for Photothermal Ablation-Chemoembolization Therapy in Rats.
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DOI：
10.1148/radiol.2016152510
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发表时间：
2016-11
期刊：
影响因子：
19.7
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Li J;Zhou M;Liu F;Xiong C;Wang W;Cao Q;Wen X;Robertson JD;Ji X;Wang YA;Gupta S;Li C
确定考布他汀 A-4 磷酸二钠 (CA4P) 是否可以增强肿瘤对负载阿霉素 (Dox)、聚乙二醇 (PEG) 包被的空心金纳米球 (HAuNS) 与碘油 (Dox@PEG-HAuNS/Lipiodol) 的混合，以改善肝细胞癌 (HCC) 的光热消融 (PTA) 化疗栓塞治疗 (CET; PTA-CET)老鼠。所有动物实验均经机构动物护理和使用委员会批准，并于2014年2月至2015年4月在45只Sprague-Dawley大鼠（雄性，12周龄）中进行。在大鼠肝脏中接种N1S1 HCC细胞后8天。将动物随机分为2组，每组10只大鼠。第1组的大鼠接受单独的PEG-HAuNS/Lipiodol的肝内动脉(IA)注射，第2组的大鼠接受CA4P的IA注射，然后5分钟后注射PEG-HAuNS/Lipiodol。将每组细分，并使用中子活化分析（NAA，n=5/时间点）对1小时或24小时切除的肿瘤和组织的Au含量进行定量。五只大鼠接受 CA4P 加 PEG-[64Cu]-HAuNS/Lipiodol 治疗并接受 μPET/CT。在另一项研究中，比较了 3 组，每组 6 只大鼠，分别接受 IA 注射生理盐水（对照组）、CA4P 加 Dox@PEG-HAuNS/Lipiodol（CET 组）或 CA4P 加 Dox@PEG-HAuNS/Lipiodol 加近红外照射（PTA-CET 组）。在激光照射期间记录温度。结果通过尸检组织病理学和/或放射自显影术进行了验证。 Wilcoxon秩和检验用于检验组间差异，Pearson相关分析用于评估相关性。在 1 小时（P<0.03）和 24 小时（P<0.01）时，CA4P 预处理的肿瘤中 PEG-HAuNS 的摄取均显着高于未 CA4P 预处理的肿瘤。在CA4P治疗组中，1小时和24小时时肿瘤与肝脏的PEG-HAuNS摄取比率分别为5.63±3.09和1.68±0.77，在非CA4P治疗组中分别为1.29±2.40和0.14±0.11。 μPET/CT 清晰地描绘出肿瘤，从而实现定量成像分析。激光照射使肿瘤和邻近肝脏的温度分别升高至 60°C 和 43°C。治疗后10 d，PTA-CET组、CET组和对照组肿瘤体积分别为1.68±1.01、3.96±1.75和6.13±2.27 cm3，PTA-CET组与其他组比较差异有统计学意义（P<0.05）。 CA4P预处理导致更高浓度的Dox@PEG-HAuNS被捕获在肿瘤内，从而增强PTA-CET在大鼠中的抗HCC功效。
To determine if combretastatin A-4 phosphate disodium (CA4P) can enhance the tumor uptake of doxorubicin (Dox)-loaded, polyethylene glycol (PEG)-coated hollow gold nanospheres (HAuNS) mixed with Lipiodol (Dox@PEG-HAuNS/Lipiodol) for improved photothermal ablation (PTA)-chemoembolization therapy (CET; PTA-CET) of hepatocellular carcinoma (HCC) in rats. All animal experiments were approved by the Institutional Animal Care and Use Committee, and were performed in 45 Sprague-Dawley rats (male, 12 weeks old) from Feb. 2014 to April 2015. Eight days after inoculation of N1S1 HCC cells in the liver of rats. Animals were randomly divided into 2 groups of 10 rats each. Rats in group 1 received intrahepatic arterial (IA) injection of PEG-HAuNS/Lipiodol alone, and rats in group 2 received IA injection of CA4P followed by PEG-HAuNS/Lipiodol 5 min later. Each group was subdivided, and the Au content of tumors and tissues excised at 1 h or at 24 h was quantified using neutron activation analysis (NAA, n=5/time point). Five rats received CA4P plus PEG-[64Cu]-HAuNS/Lipiodol and underwent μPET/CT. In a separate study, therapeutic effects were compared among 3 groups of 6 rats each that received IA injection of saline (control group), CA4P plus Dox@PEG-HAuNS/Lipiodol (CET group), or CA4P plus Dox@PEG-HAuNS/Lipiodol plus near-infrared irradiation (PTA-CET group). Temperature was recorded during laser irradiation. Findings were verified with postmortem histopathology and/or autoradiography. Wilcoxon rank-sum test was used to test the difference between groups, Pearson correlation analyses were performed to evaluate correlations. PEG-HAuNS uptake in CA4P-pretreated tumors was significantly higher than that in non–CA4P-pretreated tumors at both 1 h (P<0.03) and 24 h (P<0.01). The tumor-to-liver PEG-HAuNS uptake ratios at 1 h and 24 h were 5.63±3.09 and 1.68±0.77, respectively, in the CA4P-treated group and 1.29±2.40 and 0.14±0.11, respectively, in the non–CA4P-treated group. μPET/CT clearly delineated the tumors, enabling quantitative imaging analysis. Laser irradiation increases temperature to 60°C and 43°C in the tumor and adjacent liver, respectively. Tumor volumes 10 d after therapy were 1.68±1.01, 3.96±1.75, and 6.13±2.27 cm3 in the PTA-CET, CET, and control groups, respectively, with significant differences between the PTA-CET group and other groups (P<0.05). CA4P pretreatment causes a higher concentration of Dox@PEG-HAuNS to be trapped inside the tumor, thereby enhancing the anti-HCC efficacy of PTA-CET in rats.
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聚乙二醇包被的空心金纳米球的药代动力学、清除率和生物安全性
影响因子：
10
作者：
You J;Zhou J;Zhou M;Liu Y;Robertson JD;Liang D;Van Pelt C;Li C
通讯作者：
Li C
影响因子：
17.4
作者：
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影响因子：
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作者：
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Zhang, Jian
DOI：
10.1016/s0360-3016(01)01742-4
发表时间：
2001-11-15
影响因子：
7
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Horsman, Michael R.