{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:54:13Z","timestamp":1780937653521,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Program for International Science and Technology Cooperation Projects of China","award":["2020YFE0201700"],"award-info":[{"award-number":["2020YFE0201700"]}]},{"name":"Key Program for International Science and Technology Cooperation Projects of China","award":["1262000102"],"award-info":[{"award-number":["1262000102"]}]},{"name":"Innovation Leading Talents Short-term Program of Jiangxi Province, China","award":["2020YFE0201700"],"award-info":[{"award-number":["2020YFE0201700"]}]},{"name":"Innovation Leading Talents Short-term Program of Jiangxi Province, China","award":["1262000102"],"award-info":[{"award-number":["1262000102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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\u2013guest 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics15010142","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:23:06Z","timestamp":1672626186000},"page":"142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Lactone Stabilized by Crosslinked Cyclodextrin Metal-Organic Frameworks to Improve Local Bioavailability of Topotecan in Lung Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Ting","family":"Xiong","sequence":"first","affiliation":[{"name":"Key Laboratory of Modern Preparation of TCM, Jiangxi University of Traditional Chinese Medicine, Ministry of Education, Nanchang 330004, China"},{"name":"Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Guo","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeying","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"University of the Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huipeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"University of the Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Modern Preparation of TCM, Jiangxi University of Traditional Chinese Medicine, Ministry of Education, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Modern Preparation of TCM, Jiangxi University of Traditional Chinese Medicine, Ministry of Education, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0410-0052","authenticated-orcid":false,"given":"Jiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Modern Preparation of TCM, Jiangxi University of Traditional Chinese Medicine, Ministry of Education, Nanchang 330004, China"},{"name":"Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer Statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. 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