ATP-responsive hollow nanocapsules for DOX/GOx delivery to enable tumor inhibition with suppressed P-glycoprotein
ATP-responsive hollow nanocapsules for DOX/GOx delivery to enable tumor inhibition with suppressed P-glycoprotein
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DOI：
10.1007/s12274-020-3071-7
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发表时间：
2020-09
期刊：
影响因子：
9.9
通讯作者：
Huimin Zhu;Guodong Cao;Yike Fu;Chao Fang;Q. Chu;Xiang Li;Yulian Wu;G. Han
中科院分区：
文献类型：
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作者：
Huimin Zhu;Guodong Cao;Yike Fu;Chao Fang;Q. Chu;Xiang Li;Yulian Wu;G. Han
由于p -糖蛋白（p -糖蛋白）介导的药物外排，多药耐药（MDR）限制了化疗的疗效，而目前抑制p -糖蛋白表达的方法面临着内在的挑战，如转染量低、毒性高和特异性差。本研究合成了可与三磷酸腺苷（ATP）反应有效降解的中空铁-单宁酸复合物纳米胶囊（HFe-TA），用于递送葡萄糖氧化酶（GOx）和阿霉素（DOX）用于肿瘤治疗。研究结果表明，由于HFe-TA降解和gox介导的葡萄糖消耗的共同作用，细胞内ATP显著减少。在ATP下调的同时，肿瘤细胞的P-gp表达明显受到抑制，从而促进DOX在细胞内的蓄积和抗癌作用。此外，GOx氧化葡萄糖过程的副产物促进了HFe-TA释放的Fe离子生成•OH。因此，由于级联反应的协同作用，负载DOX和GOx的HFe-TA纳米胶囊在体外对肿瘤具有显著的抑制作用。因此，这项研究为有效抑制肿瘤提供了另一种治疗平台，具有克服内在耐多药的潜力。
Multidrug resistance (MDR) restricts chemotherapy efficacy due to P-glycoprotein (P-gp) mediated drug efflux, whereas current approaches to suppressing P-gp expression suffer from intrinsic challenges, such as low transfection, high toxicity and poor specificity. Here, hollow ferric-tannic acid complex nanocapsules (HFe-TA), which can be effectively degraded by the reaction with adenosine triphosphate (ATP), are synthesized for the delivery of glucose oxidase (GOx) and doxorubicin (DOX) for tumor treatment. The findings indicate that the intracellular ATP is significantly decreased due to the combined effect of HFe-TA degradation and GOx-mediated glucose consumption. Along with this ATP down-regulation, P-gp expression of tumor cells is suppressed remarkably, which in turn promotes the intracellular accumulation and anticancer efficacy of DOX. In addition, the production of•OH by Fe ions released from HFe-TA is promoted by the by-products of the oxidation of glucose process by GOx. In consequence, HFe-TA nanocapsules loaded with DOX and GOx enable significant inhibition effect to tumors bothin vitroandin vivodue to the synergistic effect of cascade reactions. This study has therefore provided an alternative therapeutic platform for effective tumor inhibition with the potential in overcoming intrinsic MDR.