title: Hypoxia-directed and activated theranostic agent: Imaging and treatment of solid tumor.
abstract: Hypoxia, a distinguished feature of various solid tumors, has been considered as a key marker for tumor progression. Inadequate vasculature and high interstitial pressures result in relatively poor drug delivery to these tumors. Herein, we developed an antitumor theranostic agent, 4, which is activated in hypoxic conditions and can be used for the diagnosis and treatment of solid tumors. Compound 4, bearing biotin, a tumor-targeting unit, and SN38, an anticancer drug, proved to be an effective theranostic agent for solid tumors. SN38 plays a dual role: as an anticancer drug for therapy and as a fluorophore for diagnosis, thus avoids an extra fluorophore and limits cytotoxicity. Compound 4, activated in the hypoxic environment, showed high therapeutic activity in A549 and HeLa cells and spheroids. In vivo imaging of solid tumors confirmed the tumor-specific localization, deep tissue penetration and activation of compound 4, as well as the production of a strong anticancer effect through the inhibition of tumor growth in a xenograft mouse model validating it as a promising strategy for the treatment of solid tumors.
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
authors.forename: Eun-Joong
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Laboratory of Stem Cells and Tissue Regeneration, College of Life Sciences & Biotechnology, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Jiyou
authors.initials: J
authors.lastname: Han
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Weon Sup
authors.initials: WS
authors.lastname: Shin
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Amrita Centre for Industrial Research & Innovation, Amrita School of Engineering, Amrita University, Ettimadai, Coimbatore 641 112, India. Electronic address: b_sankarprasad@cb.amrita.edu.
authors.forename: Sankarprasad
authors.initials: S
authors.lastname: Bhuniya
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Republic of Korea. Electronic address: jongskim@korea.ac.kr.
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute, Cheongju 28119, Republic of Korea. Electronic address: kshong@kbsi.re.kr.
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Hong
mesh_terms: D000072283:A549 Cells; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D005456:Fluorescent Dyes; D006367:HeLa Cells; D006801:Humans; D000077146:Irinotecan; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D010100:Oxygen / Q000737:chemistry; D000068936:Theranostic Nanomedicine / Q000379:methods*; D016896:Treatment Outcome; D000072258:Tumor Hypoxia
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005456:Fluorescent Dyes; D000077146:Irinotecan; D010100:Oxygen; D002166:Camptothecin
keywords: Anti-tumor; Hypoxia; Prodrug; Solid tumor; Theranostic