Bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles: preparation, cellular uptake, tissue distribution, and anticancer activity.
Bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles: preparation, cellular uptake, tissue distribution, and anticancer activity.
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DOI：
10.2147/ijn.s32063
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发表时间：
2012
影响因子：
8
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Yin P;Wang Y;Qiu Y;Hou L;Liu X;Qin J;Duan Y;Liu P;Qiu M;Li Q
近年来的研究表明蟾蜍灵具有良好的抗肿瘤作用，但毒性大、水溶性差、半衰期短、治疗窗窄、毒性剂量接近治疗剂量等都限制了其临床应用。本研究旨在确定由甲氧基聚乙二醇（mPEG）、聚乳酸-羟基乙酸共聚物（PLGA）、聚-L-赖氨酸（PLL）和环甘氨酸-甘氨酸-天冬氨酸（cRGD）制成的负载蟾蜍灵的纳米粒（NPs），即负载蟾蜍灵的mPEG-PLGA-PLL-cRGD纳米粒（BNPs）在SW 620结肠癌荷瘤小鼠中的靶向效力。BNP显示均匀的尺寸。在体外研究了这些纳米粒的大小、形状、Zeta电位、载药量、包封率和释放。测试了BNPs在体内的肿瘤靶向、细胞摄取和生长抑制作用。BNP具有均匀的尺寸，平均粒度为164 ± 84 nm，ζ电位为2.77 mV。包封率为81.7% ± 0.89%，载药量为3.92% ± 0.16%。体外细胞毒性研究结果表明，虽然空白纳米粒是无毒的，但它们增强了蟾毒灵的细胞毒性。药物释放实验表明，药物的释放是延长和持续的。激光共聚焦扫描显微镜结果表明，BNPs能有效地与人脐静脉内皮细胞结合。在SW 620异种移植瘤小鼠模型中，BNPs可以有效地靶向体内肿瘤。BNP在预防肿瘤生长方面比其他NP显著更有效。BNPs粒径分布均匀，性质稳定，具有缓释和肿瘤靶向作用。在体外和体内，BNPs显著抑制结肠癌生长。作为一种新型的药物载体系统，BNPs有望成为结肠癌的靶向治疗药物。
Recent studies have shown that bufalin has a good antitumor effect but has high toxicity, poor water solubility, a short half-life, a narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study aimed to determine the targeting efficacy of nanoparticles (NPs) made of methoxy polyethylene glycol (mPEG), polylactic-co-glycolic acid (PLGA), poly-L-lysine (PLL), and cyclic arginine-glycine-aspartic acid (cRGD) loaded with bufalin, ie, bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles (BNPs), in SW620 colon cancer-bearing mice. BNPs showed uniform size. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these nanoparticles were studied in vitro. The tumor targeting, cellular uptake, and growth-inhibitory effect of BNPs in vivo were tested. BNPs were of uniform size with an average particle size of 164 ± 84 nm and zeta potential of 2.77 mV. The encapsulation efficiency was 81.7% ± 0.89%, and the drug load was 3.92% ± 0.16%. The results of in vitro cytotoxicity studies showed that although the blank NPs were nontoxic, they enhanced the cytotoxicity of bufalin in BNPs. Drug release experiments showed that the release of the drug was prolonged and sustained. The results of confocal laser scanning microscopy indicated that BNPs could effectively bind to human umbilical vein endothelial cells. In the SW620 xenograft mice model, the BNPs could effectively target the tumor in vivo. The BNPs were significantly more effective than other NPs in preventing tumor growth. BNPs had even size distribution, were stable, and had a slow-releasing and tumor-targeting effect. BNPs significantly inhibited colon cancer growth in vitro and in vivo. As a novel drug carrier system, BNPs are a potentially promising targeting treatment for colon cancer.