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通过将抗αv 整合素抗体连接到载多柔比星的人血清白蛋白纳米粒上增强药物靶向性。

Enhanced drug targeting by attachment of an anti alphav integrin antibody to doxorubicin loaded human serum albumin nanoparticles.

机构信息

Fraunhofer Institute for Biomedical Engineering, D-66386 St.Ingbert, Germany.

出版信息

Biomaterials. 2010 Mar;31(8):2388-98. doi: 10.1016/j.biomaterials.2009.11.093. Epub 2009 Dec 23.

Abstract

Specific transport of anti-cancer drugs into tumor cells may result in increased therapeutic efficacy and decreased adverse events. Expression of alphavbeta3 integrin is enhanced in various types of cancer and monoclonal antibodies (mAbs) directed against alphavbeta3 integrins hold promise for anti-cancer therapy. DI17E6 is a monoclonal antibody directed against alphav integrins that inhibits growth of melanomas in vitro and in vivo and inhibits angiogenesis due to interference with alphavbeta3 integrins. Here, DI17E6 was covalently coupled to human serum albumin nanoparticles. Resulting nanoparticles specifically targeted alphavbeta3 integrin positive melanoma cells. Moreover, doxorubicin loaded DI17E6 nanoparticles showed increased cytotoxic activity in alphavbeta3-positive melanoma cells than the free drug. Therefore, DI17E6-coupled human serum albumin nanoparticles represent a potential delivery system for targeted drug transport into alphavbeta3-positive cells.

摘要

将抗癌药物特异性地输送到肿瘤细胞中可能会提高治疗效果并降低不良反应的发生。在各种类型的癌症中,αvβ3 整合素的表达增强,针对 αvβ3 整合素的单克隆抗体(mAbs)为癌症治疗带来了希望。DI17E6 是一种针对 αv 整合素的单克隆抗体,可在体外和体内抑制黑色素瘤的生长,并通过干扰 αvβ3 整合素抑制血管生成。在这里,DI17E6 被共价偶联到人血清白蛋白纳米颗粒上。由此产生的纳米颗粒特异性地靶向 αvβ3 整合素阳性的黑色素瘤细胞。此外,载有阿霉素的 DI17E6 纳米颗粒在 αvβ3 阳性黑色素瘤细胞中的细胞毒性活性高于游离药物。因此,DI17E6 偶联的人血清白蛋白纳米颗粒代表了一种将药物靶向输送到 αvβ3 阳性细胞的潜在递送系统。

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