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Lactone Stabilized by Crosslinked Cyclodextrin Metal-Organic Frameworks to Improve Local Bioavailability of Topotecan in Lung Cancer

文献类型：期刊论文

作者Xiong, Ting1,2,3; Guo, Tao2; He, Yaping4; Cao, Zeying2,5; Xu, Huipeng2,5; Wu, Wenting1; Wu, Li2; Zhu, Weifeng1; Zhang, Jiwen1,2,3
刊名PHARMACEUTICS
出版日期2023
卷号15期号:1页码:14
关键词topotecan crosslinked cyclodextrin metal-organic framework stability melanoma lung metastasis local bioavailability
DOI10.3390/pharmaceutics15010142
通讯作者Zhu, Weifeng(zwf0322@126.com) ; Zhang, Jiwen(jwzhang@simm.ac.cn)
英文摘要The protection of unstable anticancer molecules and their delivery to lesions are challenging issues in cancer treatment. Topotecan (TPT), a classic cytotoxic drug, is widely used for treating refractory lung cancer. However, the therapeutic effects of TPT are jeopardized by its active lactone form that is intrinsically hydrolyzed in physiological fluids, resulting in low bioavailability. Herein, the TPT-loaded crosslinked cyclodextrin metal-organic framework (TPT@CL-MOF) was engineered to improve the local bioavailability of TPT for the treatment of lung cancer. CL-MOF exhibited the efficient loading (12.3 wt%) of TPT with sustained release characteristics. In particular the formulation offered excellent protection in vitro against hydrolysis and increased the half-life of TPT from approximately 0.93 h to 22.05 h, which can be attributed to the host-guest interaction between cyclodextrin and TPT, as confirmed by molecular docking. The TPT@CL-MOF could effectively kill the cancer cells and inhibit the migration and invasion of B16F10 cells in vitro. Moreover, TPT@CL-MOF was efficiently distributed in the lungs after intravenous administration. In an in vivo study using a B16F10 pulmonary metastatic tumor model, TPT@CL-MOF significantly reduced the number and size of metastatic lung nodules at a reduced low dose by five times, and no noticeable side effects were observed. Therefore, this study provides a possible alternative therapy for the treatment of lung cancer with the camptothecin family drugs or other unstable therapeutically significant molecules.
WOS关键词DRUG-DELIVERY ; CD-MOF ; ENCAPSULATION ; NANOMEDICINE ; METASTASIS ; HYDROLYSIS ; CURCUMIN ; AGENTS ; CELLS
资助项目Key Program for International Science and Technology Cooperation Projects of China[2020YFE0201700] ; Innovation Leading Talents Short-term Program of Jiangxi Province, China[1262000102]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者MDPI
WOS记录号WOS:000915991600001
源URL[http://119.78.100.183/handle/2S10ELR8/303576]  
专题中国科学院上海药物研究所
通讯作者Zhu, Weifeng; Zhang, Jiwen
作者单位1.Jiangxi Univ Tradit Chinese Med, Key Lab Modern Preparat TCM, Minist Educ, Nanchang 330004, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 201203, Peoples R China
3.Shenyang Pharmaceut Univ, Coll Pharm, Shenyang 110016, Peoples R China
4.Zhengzhou Univ, Affiliated Hosp 1, Dept Pharm, Zhengzhou 450052, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Xiong, Ting,Guo, Tao,He, Yaping,et al. Lactone Stabilized by Crosslinked Cyclodextrin Metal-Organic Frameworks to Improve Local Bioavailability of Topotecan in Lung Cancer[J]. PHARMACEUTICS,2023,15(1):14.
APA Xiong, Ting.,Guo, Tao.,He, Yaping.,Cao, Zeying.,Xu, Huipeng.,...&Zhang, Jiwen.(2023).Lactone Stabilized by Crosslinked Cyclodextrin Metal-Organic Frameworks to Improve Local Bioavailability of Topotecan in Lung Cancer.PHARMACEUTICS,15(1),14.
MLA Xiong, Ting,et al."Lactone Stabilized by Crosslinked Cyclodextrin Metal-Organic Frameworks to Improve Local Bioavailability of Topotecan in Lung Cancer".PHARMACEUTICS 15.1(2023):14.

入库方式： OAI收割

来源：上海药物研究所

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