Glutathione detonated and pH responsive nano-clusters of Au nanorods with a high dose of DOX for treatment of multidrug resistant cancer
Glutathione detonated and pH responsive nano-clusters of Au nanorods with a high dose of DOX for treatment of multidrug resistant cancer
复制标题
谷胱甘肽引爆和 pH 响应的金纳米棒纳米簇与高剂量 DOX 用于治疗多重耐药癌症
DOI：
10.1016/j.actbio.2018.06.012
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发表时间：
2018-07-15
影响因子：
9.7
通讯作者：
Guo, Shengrong
中科院分区：
文献类型：
--
作者：
Wang, Yun;Wang, Feihu;Guo, Shengrong
纳米给药系统由于载药量低、药物过早释放和多药耐药（MDR）等原因，其对肿瘤的治疗效果往往受到影响。在此，我们报告了谷胱甘肽引爆和pH响应性纳米簇的Au纳米棒（AuNR）与化疗阿霉素（DOX）和预化疗增敏剂聚姜黄素治疗MCF-7/ADR细胞。通过乳液/溶剂蒸发技术，通过与DOX和两亲性聚（姜黄素-co-二硫代二丙酸）-b-生物素化聚（乙二醇）缀合的AuNR自组装制备纳米簇，称为AuNR簇。AuNR簇具有高载药量（31.5%DOX），在生理pH下表现出比它们的单个AuNR更好的水溶性和稳定性。AuNR簇可以在谷胱甘肽（GSH）的细胞内浓度水平（5 mM）下被引爆为其单独的AuNR，并且在酸性pH（pH 6.8或5.0）下被触发以释放DOX，这有效地促进了DOX的细胞摄取（607相对于356 a.u.对于12 h的AuNR）和抑制DOX流出（471.33 vs 39.17 a.u. 24小时时的游离DOX）。DOX对MCF-7/ADR细胞的IC_（50）值为4.15 μ g/mL，远低于游离DOX的IC_（50）值（90.97 μ g/mL）。在808 nm激光照射下，AuNR团簇比相应的AuNR团簇具有更强的光热效应，并表现出更强的抗肿瘤作用（IC 50：2.61 μ g/mL）。(C)2018 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Effects of nanosized drug delivery systems on cancer are often compromised due to their low drug loadings, premature drug release and multi-drug resistance (MDR). Herein, we reported a glutathione detonated and pH responsive nano-cluster of Au nanorods (AuNRs) with chemotherapeutic doxorubicin (DOX) and pre-chemosensitizer polycurcumin to treat MCF-7/ADR cells. The nano-cluster was prepared by self-assembling of AuNRs conjugated with DOX and amphiphilic poly(curcumin-co-dithiodipropionic acid)-b-biotinylated poly(ethylene glycol) via an emulsion/solvent evaporation technique, termed AuNR Cluster. The AuNR Cluster had a high drug loading (31.5% DOX), presenting much better aqueous solubility and stability at physiological pH than their individual AuNRs. The AuNR Cluster could be detonated to be their individual AuNRs at an intracellular concentration level of glutathione (GSH) (5 mM) and triggered to release DOX at an acidic pH (pH 6.8 or 5.0), which effectively facilitated cellular uptake of DOX (607 vs 356 a.u. for AuNRs at 12 h) and inhibited DOX efflux (471.33 vs 39.17 a.u. for free DOX at 24 h). The IC50 value of DOX against MCF-7/ADR cells for AuNR Cluster was 4.15 mu g/mL, much lower than that for free DOX (90.97 mu g/mL). The AuNR Cluster took much more photothermal effects than their corresponding AuNRs and presented enhanced anti-tumor effect (IC50: 2.61 mu g/mL) under 808 nm laser irradiation. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.