Doxorubicin loaded polymeric gold nanoparticles targeted to human folate receptor upon laser photothermal therapy potentiates chemotherapy in breast cancer cell lines
Doxorubicin loaded polymeric gold nanoparticles targeted to human folate receptor upon laser photothermal therapy potentiates chemotherapy in breast cancer cell lines
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DOI：
10.1016/j.jphotobiol.2015.05.008
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发表时间：
2015-08-01
影响因子：
5.4
通讯作者：
Vasanthakumar, Geetha
中科院分区：
文献类型：
--
作者：
Banu, Hussaina;Sethi, Dipinder Kaur;Vasanthakumar, Geetha
目前的研究主要集中在应用叶酸偶联和阿霉素负载的聚合金纳米粒(GNPs)来靶向治疗叶酸受体高表达的乳腺癌，并辅以激光光热治疗。本论文将叶酸修饰的GNPs、阿霉素类药物和聚乙二醇类药物作为叶酸受体靶向多柔比星靶向癌细胞的载体。随后，用激光对GNPs进行光激发，以介导癌细胞内的热疗。体外研究验证了与游离药物治疗相比，叶酸偶联和多柔比星多聚GNP介导的化疗和光热治疗的联合方案的疗效；与低叶酸受体表达的MCF-7乳腺癌细胞相比，联合方案对表面叶酸受体表达增加的MDA-MB-231乳腺癌细胞显示出更好的治疗效果。用荧光显微镜观察细胞死亡机制。免疫分析显示促凋亡蛋白P53表达上调，抗凋亡蛋白BCI-2表达下调。总之，这些结果表明，叶酸标记的阿霉素GNPs是一个有吸引力的靶向传递阿霉素的平台，是适合于光热癌症治疗的试剂。(C)2015爱思唯尔B.V.保留所有权利。
The current research focuses on the application of folate conjugated and doxorubicin loaded polymeric gold nanoparticles (GNPs) for the targeted treatment of folate receptor overexpressing breast cancers, augmented by adjunctive laser photothermal therapy. Herein, GNPs surface modified with folate, drug doxorubicin and polyethylene glycol were engineered and were used as vehicles for folate receptor targeted delivery of doxorubicin into cancer cells. Subsequently, the GNPs were photo-excited using laser light for mediating hyperthermia in the cancer cells. In vitro studies were performed to validate the efficacy of the combined modality of folate conjugated and doxorubicin loaded polymeric GNP mediated chemotherapy followed by photothermal therapy in comparison to treatment with free drug; and the combination modality showed better therapeutic efficacy than that of plain doxorubicin treatment in MDA-MB-231 breast cancer cells that express increased levels of surface folate receptors when compared to MCF-7 breast cancer cells that express low levels of folate receptor. The mechanism of cell death was investigated using fluorescent microscopy. Immunoassays showed the up-regulation of the pro-apoptotic protein p53 and down-regulation of the anti-apoptotic protein BcI-2. Collectively, these results suggest that the folate tagged doxorubicin loaded GNPs are an attractive platform for targeted delivery of doxorubicin and are agents suitable for photothermal cancer therapy. (C) 2015 Elsevier B.V. All rights reserved.