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协同铂(II)前药纳米颗粒增强乳腺癌治疗。

Synergistic Platinum(II) Prodrug Nanoparticles for Enhanced Breast Cancer Therapy.

机构信息

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Mol Pharm. 2020 Apr 6;17(4):1300-1309. doi: 10.1021/acs.molpharmaceut.9b01318. Epub 2020 Feb 24.

Abstract

Chemotherapy still accounts for a large proportion of the treatments of tumors, but the drug resistance and side effects caused by long-term chemotherapy should not be underestimated. In this work, the drug combination strategy has been widely developed to overcome the side effects brought by the use of single drugs and improve the therapeutic effect. However, in clinical applications, the co-delivery of drugs is very difficult, and different kinetics due to different drug properties will lead to a decrease in efficacy. Thus, the design of novel antitumor therapeutic agents, including new platinum agents, represents an area in need of urgent attention. Our investigation implies a promising strategy for the design of a platinum prodrug to enhance the treatment of breast cancer. A dual-drug delivery nanoparticle was developed for enhanced treatment of breast cancer based on a two-into-one co-delivery strategy. Through the synergistic effect of released cisplatin hydrate and tolfenamic acid (COX-2 inhibitor) from the coordination prodrug, the tumor growth is significantly suppressed, and the survival time is greatly extended in breast tumor-bearing mice.

摘要

化疗仍然在肿瘤治疗中占有很大比例,但长期化疗引起的药物耐药性和副作用不容小觑。在这项工作中,药物联合策略已被广泛开发,以克服单药使用带来的副作用,并提高治疗效果。然而,在临床应用中,药物的共递药非常困难,由于不同药物性质的不同动力学会导致疗效下降。因此,设计新型抗肿瘤治疗剂,包括新型铂类药物,是一个急需关注的领域。我们的研究为设计铂前药增强乳腺癌治疗提供了一种有前途的策略。基于二合一共递药策略,开发了一种双药物递送纳米粒子,用于增强乳腺癌的治疗。通过来自配位前药的释放顺铂水合物和托芬酸(COX-2 抑制剂)的协同作用,显著抑制肿瘤生长,并大大延长荷瘤小鼠的生存时间。

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