pH-sensitive pullulan-based nanoparticle carrier for adriamycin to overcome drug-resistance of cancer cells
pH-sensitive pullulan-based nanoparticle carrier for adriamycin to overcome drug-resistance of cancer cells
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pH敏感的支链淀粉纳米颗粒载体阿霉素克服癌细胞耐药性
DOI：
10.1016/j.carbpol.2014.05.057
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发表时间：
2014-10-13
影响因子：
11.2
通讯作者：
Zhang, Ning
中科院分区：
文献类型：
--
作者：
Guo, Hua;Liu, Yuanyuan;Zhang, Ning
以普鲁兰多糖为原料，通过偶联尿刊酸合成取代度为8.2%的O-尿刊酰基普鲁兰多糖（URPA）。通过透析法制备的URPA纳米颗粒具有球形形状，平均直径为156.8 ± 16.8 nm。阿霉素（ADR）被成功地负载到URPA纳米粒中，并表现出pH敏感的体外释放特性。KIT法检测表明，ADR/URPA纳米粒对MCF-7/ADR耐药细胞的毒性明显高于游离ADR，逆转指数高达9.6。流式细胞仪和共聚焦显微镜结果表明，URPA纳米粒能有效地促进ADR在MCF-7/ADR细胞中的蓄积和滞留，并成功地将ADR递送到细胞核中。ADR/URPA纳米粒对MCF-7/ADR细胞耐药性的逆转作用可能与其进入细胞和细胞内药物释放机制有关。(C)2014爱思唯尔有限公司版权所有。
Urocanic acid was conjugated to pullulan to synthesize O-urocanyl pullulan (URPA) with degree of substitution (DS) of 8.2%. URPA nanoparticles prepared by dialysis method had spherical shapes and a mean diameter of 156.8 +/- 16.8 nm. Adriamycin (ADR) was successfully loaded into URPA nanoparticles and exhibited pH-sensitive in vitro release property. KIT assay showed that ADR-loaded URPA (ADR/URPA) nanoparticles had a significant higher toxicity against drug resistant MCF-7/ADR cells than free ADR, and the reversal index reached up to 9.6. The results of flow cytometry and confocal microscopy showed that URPA nanoparticles efficiently enhanced accumulation and retention of ADR in MCF-7/ADR cells and successfully delivered ADR into cell nucleus. The reversal effect of ADR/URPA nanoparticles on the drug resistance of MCF-7/ADR cells was perhaps related with their cell entry and intracellular drug release mechanisms. (C) 2014 Elsevier Ltd. All rights reserved.