One of the major obstacles to successful chemotherapy is multi-drug resistance (MDR). A multi-drug resistant cancerous cell abnormally overexpresses membrane transporters that pump anticancer drugs out of the cell, resulting in low anticancer drug delivery efficiency. To overcome the limitation, many attempts have been performed to inhibit the abilities of efflux receptors chemically or genetically or to increase the delivery efficiency of anticancer drugs. However, the results have not yet been satisfactory. In this study, we developed nanoparticle-microbubble complexes (DOX-NPs/Ce6-MBs) by conjugating doxorubicin loaded human serum albumin nanoparticles (DOX-NPs) onto the surface of Chlorin e6 encapsulated microbubbles (Ce6-MBs) in order to maximize anticancer efficiency by overcoming MDR. Under the ultrasound irradiation, DOX-NPs and Ce6 encapsulating self-assembled liposomes or micelles were effectively delivered into the cells due to the sonoporation effect caused by the microbubble cavitation. At the same time, reactive oxygen (ROS) generated from intracellularly delivered Ce6 by laser irradiation arrested the activity of ABCG2 efflux receptor overexpressed in doxorubicin-resistant breast cancer cells (MCF-7/ADR), resulting in increased the chemotherapy efficacy. In addition, the total number of side population cells that exhibit the properties of cancer stem-like cells were also reduced by the combination of photodynamic therapy and chemotherapy. In conclusion, DOX-NPs/Ce6-MBs will provide a platform for simultaneously overcoming MDR and increasing drug delivery and therefore, treatment efficiency, under ultrasound irradiation.

中文翻译：

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通过光动力疗法相关的外排泵失活和超声介导的改善的药物递送效率来克服抗癌性。

成功化疗的主要障碍之一是多药耐药性（MDR）。耐多药癌细胞异常表达膜转运蛋白，将抗癌药泵出细胞，导致抗癌药的传递效率低下。为了克服该限制，已经进行了许多尝试以化学或遗传方式抑制外排受体的能力或增加抗癌药物的递送效率。但是，结果仍不令人满意。在这项研究中，我们通过将载有阿霉素的人血清白蛋白纳米颗粒（DOX-NPs）偶联到Chlorin e6包裹的微泡（Ce6-MBs）表面上，开发了纳米颗粒-微泡复合物（DOX-NPs / Ce6-MBs），以最大程度地发挥抗癌作用通过克服MDR来提高效率。在超声波照射下 由于微泡空化引起的声穿孔作用，将自组装脂质体或胶束的DOX-NP和Ce6封装有效地传递到细胞中。同时，通过激光照射从细胞内递送的Ce6产生的活性氧（ROS）阻止了在抗阿霉素的乳腺癌细胞（MCF-7 / ADR）中过表达的ABCG2外排受体的活性，从而提高了化疗的疗效。此外，通过光动力疗法和化学疗法的组合，还显示出具有癌干样细胞特性的侧群细胞总数。总之，DOX-NP / Ce6-MBs将提供一个平台，在超声辐射下同时克服MDR并增加药物输送，从而提高治疗效率。