期刊
MOLECULAR PHARMACEUTICS
卷 17, 期 4, 页码 1300-1309出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.9b01318
关键词
synergistic effect; combination therapy; chemotherapy; COX-2 inhibitor; cisplatin; prodrug
资金
- National Science and Technology Major Project [2017YFA0205400]
- National Natural Science Foundation of China [81773667, 81573369, 81803473]
- NSFC Projects of International Cooperation and Exchanges [811811540416]
- Fundamental Research Funds for the Central Universities [2632018PT01]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- 111 Project from the Ministry of Education of China
- State Administration of Foreign Experts Affairs of China [B16046]
- Double first-class project [CPU2018GY06]
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 in vivo 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.
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