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首页> 外文期刊>Materials science & engineering >A multi-functionalized nanocomposite constructed by gold nanorod core with triple-layer coating to combat multidrug resistant colorectal cancer
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A multi-functionalized nanocomposite constructed by gold nanorod core with triple-layer coating to combat multidrug resistant colorectal cancer

机译：由金纳米棒芯和三层涂层构成的多功能纳米复合材料，可抵抗多药耐药的结直肠癌

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Multi-drug resistance (MDR) remains the main culprit for the low survival rate of advanced colorectal cancer (CRC). Photothermal-therapy (PPT) is effective to kill MDR tumor cells, but fails to completely eradicate tumors. In this study, we prepared a nanocomposite based on gold nanorod core with triple layer coating (GNRs/mSiO(2)/PHIS/TPGS/DOX) to combat multidrug resistant (MDR) colorectal cancer via multi-strategies. We first synthesized the mesoporous silica-coated gold nanorods (GNRs/mSiO(2)), and loaded with antitumor drug doxorubicin (DOX) to realize a combination of chemo- and photothermal-therapy. To reverse DOX resistance, pH responsive poly-histidine (PHIS) was conjugated on GNRs/mSiO(2) to increase drug intracellular accumulation via efficient endo/lysosome escape; D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) was then assembled on the surface of the particles to realize drug intracellular retention by inhibition P-glycoprotein. The results showed that the nanocomposite exhibited a highly efficient photothermal conversion in the NIR region, a pH and NIR triggered drug release profile and an increment of DOX intracellular accumulation and cytotoxicity on MDR SW620/Ad300 cells. Most importantly, the nanocomposite showed the most potent antitumor efficacy without obvious systemic toxicity comparing to other control groups with either chemo- or photothermal therapy alone on SW620/Ad300 tumor bearing mice. Altogether, the successful preparation of the nanocomposite and its potent efficacy might provide evidence for the future design and develop of nano-therapeutic system in the treatment of MDR colorectal cancer.
机译：多药耐药性（MDR）仍然是晚期结直肠癌（CRC）低存活率的主要原因。光热疗法（PPT）可有效杀死MDR肿瘤细胞，但无法完全根除肿瘤。在这项研究中，我们准备了一种具有三层涂层（GNRs / mSiO（2）/ PHIS / TPGS / DOX）的金纳米棒核心纳米复合材料，以通过多种策略对抗多药耐药（MDR）大肠癌。我们首先合成了介孔二氧化硅涂层的金纳米棒（GNRs / mSiO（2）），并加载了抗肿瘤药物阿霉素（DOX），以实现化学疗法和光疗疗法的结合。为了逆转对DOX的抵抗，将pH响应的聚组氨酸（PHIS）结合在GNRs / mSiO（2）上，以通过有效的内/溶酶体逸出增加药物细胞内的积累;然后将D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）组装在颗粒表面上，以通过抑制P-糖蛋白实现药物在细胞内的保留。结果表明，该纳米复合材料在NIR区域表现出高效的光热转化，pH和NIR触发了药物释放曲线，并增加了MDR SW620 / Ad300细胞的DOX细胞内积累和细胞毒性。最重要的是，与单独使用化学或光热疗法治疗SW620 / Ad300荷瘤小鼠的其他对照组相比，纳米复合材料显示出最有效的抗肿瘤功效，而没有明显的全身毒性。总之，纳米复合材料的成功制备及其强大的功效可能为未来设计和开发用于治疗MDR大肠癌的纳米治疗系统提供证据。

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  • 来源
    《Materials science & engineering》 |2020年第2期|110224.1-110224.13|共13页
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    Tianjin Med Univ Sch Pharm Tianjbt Key Lab Technol Enabling Dev Clin Therape Tianjin 300070 Peoples R China;

    Peking Univ Hlth Sci Ctr Sch Basic Med Sci Inst Syst Biomed Beijing 100191 Peoples R China;

    St Johns Univ Coll Pharm & Hlth Sci 8000 Utopia Pkwy New York NY 11439 USA;

    Tianjin Med Univ Res Ctr Basic Med Sci Tianjin 300070 Peoples R China;

    Tianjin Med Univ Sch Pharm Tianjbt Key Lab Technol Enabling Dev Clin Therape Tianjin 300070 Peoples R China|Univ Michigan Coll Pharm 428 Church St Ann Arbor MI 48109 USA;

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    pH-responsive; Mesoporous silica; Poly-histidine; Photothermal therapy; D-alpha-tocopherol polyethylene glycol succinate;

    机译：pH响应;介孔二氧化硅聚组氨酸;光热疗法;D-α-生育酚聚乙二醇琥珀酸酯;

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