title: Design, Synthesis, and Biological Evaluation of New Cathepsin B-Sensitive Camptothecin Nanoparticles Equipped with a Novel Multifuctional Linker.
abstract: Traditional antitumor drugs such as camptothecin and paclitaxel derivatives are widely used in cancer chemotherapy. However, the major defects of those agents include severe toxicity and poor water solubility. With these in mind, a novel multifunctional linker was designed and two Cathepsin B (CTB) sensitive CPT conjugates (9a and 9b) were synthesized. Through click chemistry, additional functional group mPEG2000 can be easily introduced into these conjugates. The introduction of mPEG2000 fragment resulted in the formation of nanoparticles 1a and 1b (average particle sizes were 216.9 and 257.9 nm, respectively) with significantly increased water solubility (more than 19 000-fold). The release of therapeutic drug SN-38 in the presence of CTB was confirmed by HPLC and prodrug 1a showed potent in vitro cytotoxicity against all tested cell lines. Impressively, compared with irinotecan, CTB sensitive prodrug 1a displayed similar in vivo efficacy with remarkable decreased in vivo toxicity.
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , 3663 North Zhongshan Road, Shanghai 200062, PR China.|Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, United States.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , 3663 North Zhongshan Road, Shanghai 200062, PR China.
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Tang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , 3663 North Zhongshan Road, Shanghai 200062, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , 3663 North Zhongshan Road, Shanghai 200062, PR China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , 3663 North Zhongshan Road, Shanghai 200062, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Bao
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , 3663 North Zhongshan Road, Shanghai 200062, PR China.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Fang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , 3663 North Zhongshan Road, Shanghai 200062, PR China.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , 3663 North Zhongshan Road, Shanghai 200062, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D002166:Camptothecin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D002401:Cathepsin B / Q000378:metabolism*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D053758:Nanoparticles; D011355:Prodrugs / Q000378:metabolism; D012995:Solubility; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D000077146:Irinotecan; D002401:Cathepsin B; D002166:Camptothecin