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负载阿霉素的中空介孔ZSM-5沸石/壳聚糖椭球体作为针对骨肉瘤的pH响应型药物递送系统

Hollow mesoporous ZSM-5 zeolite/chitosan ellipsoids loaded with doxorubicin as pH-responsive drug delivery systems against osteosarcoma.

作者信息

Wen Xi, Yang Fan, Ke Qin-Fei, Xie Xue-Tao, Guo Ya-Ping

机构信息

The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China.

出版信息

J Mater Chem B. 2017 Oct 14;5(38):7866-7875. doi: 10.1039/c7tb01830d. Epub 2017 Sep 26.

Abstract

The toxic risks and adverse effects of anticancer drugs on healthy tissues limit their wide clinical application. Herein, we for the first time fabricated hollow mesoporous ZSM-5/chitosan ellipsoids loaded with doxorubicin (HM-ZSM-5/CS/DOX) as pH-responsive drug delivery systems against osteosarcoma. The HM-ZSM-5 ellipsoids including a hollow core and a mesoporous shell could efficiently load DOX drugs with a loading efficiency of 95.8%. The CS layer was uniformly distributed on the HM-ZSM-5 ellipsoids that contributed to the pH-responsive release of DOX drugs. The controlled DOX release kinetics from the HM-ZSM-5/CS/DOX ellipsoids was fitted well with the Korsmeyer-Peppas model. The HM-ZSM-5/CS/DOX ellipsoids exhibited good biocompatibility due to the low DOX release rate in the neutral media that simulated healthy tissues or blood. Moreover, the cellular uptake of the HM-ZSM-5/CS/DOX ellipsoids took place in tumor cells, and the quick release of DOX significantly promoted the apoptosis of MG63 cells. The levels of MDA, LDH and CK markers for the HM-ZSM-5/CS/DOX group were lower than those for the free DOX group, suggesting no systemic toxicity to the heart. Therefore, the HM-ZSM-5/CS/DOX ellipsoids as novel pH-responsive drug delivery systems can effectively treat osteosarcoma without systemic toxicity.

摘要

抗癌药物对健康组织的毒性风险和不良反应限制了它们在临床上的广泛应用。在此,我们首次制备了负载阿霉素的中空介孔ZSM-5/壳聚糖椭球体(HM-ZSM-5/CS/DOX)作为针对骨肉瘤的pH响应型药物递送系统。具有中空核和介孔壳的HM-ZSM-5椭球体能够高效负载阿霉素,负载效率为95.8%。壳聚糖层均匀分布在HM-ZSM-5椭球体上,有助于阿霉素的pH响应型释放。HM-ZSM-5/CS/DOX椭球体的阿霉素控释动力学与Korsmeyer-Peppas模型拟合良好。由于在模拟健康组织或血液的中性介质中阿霉素释放速率较低,HM-ZSM-5/CS/DOX椭球体表现出良好的生物相容性。此外,HM-ZSM-5/CS/DOX椭球体在肿瘤细胞中发生细胞摄取,阿霉素的快速释放显著促进了MG63细胞的凋亡。HM-ZSM-5/CS/DOX组的丙二醛、乳酸脱氢酶和肌酸激酶标志物水平低于游离阿霉素组,表明对心脏无全身毒性。因此,HM-ZSM-5/CS/DOX椭球体作为新型pH响应型药物递送系统可有效治疗骨肉瘤且无全身毒性。

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