title: An activatable prodrug for the treatment of metastatic tumors.
abstract: Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential antimetastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2, selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective antitumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anticancer drug, SN-38.
authors.affiliation: Division of MR Research, Korea Basic Science Institute , Cheongju 363-883, Korea.
authors.forename: Eun-Joong
authors.initials: EJ
authors.lastname: Kim
authors.forename: Sankarprasad
authors.initials: S
authors.lastname: Bhuniya
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Chaejoon
authors.initials: C
authors.lastname: Cheong
authors.forename: Sukhendu
authors.initials: S
authors.lastname: Maiti
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Hong
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D000077146:Irinotecan; D006861:Hydrogen Peroxide; D002166:Camptothecin