title: Liposomal Texaphyrin Theranostics for Metastatic Liver Cancer.
abstract: Reported here is a new theranostic agent, 1, which consists of a Gd3+-texaphyrin core conjugated to a doxorubicin prodrug via a disulfide bond. Conjugate 1 was designed to undergo cleavage in the presence of glutathione (GSH), a species typically upregulated in cancer cells. As prepared, conjugate 1 displays no appreciable fluorescence. However, when exposed to excess GSH an increase in the fluorescence intensity at 592 nm is observed that is ascribed to release of free doxorubicin. To improve the solubility and enhance the tumor targeting of 1, it was loaded into folate-receptor-targeted liposomes to produce FL-1 (for folate liposome loaded with 1). As inferred from both fluorescence turn on studies and independent HPLC analyses, FL-1 was found to undergo selective uptake and cleavage to release free Dox in the KB and CT26 cell lines, which express folate receptors on the cell surface, relative to the HepG2 and NIH3T3 cell lines, which show low expression of those receptors. FL-1 was found to produce a greater antiproliferative effect in the case of the KB and CT26 cell lines as compared to that in the HepG2 and NIH3T3 cell lines. FL-1 was also found to provide enhanced magnetic resonance imaging in vivo under conditions of T1contrast in the early stage of metastatic cancer progression. Finally, time-dependent tumor regrowth studies involving both subcutaneous and metastatic liver cancer mouse models revealed that FL-1 is capable of reducing the tumor burden in vivo.
authors.affiliation: Department of Chemistry, Sookmyung Women's University , Seoul 04310, Korea.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute , Cheongju 28119, Korea.|Department of Biomedical Engineering, School of Medicine, Kyung Hee University , Seoul 02447, Korea.
authors.forename: Eun-Joong
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute , Cheongju 28119, Korea.|Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon 34141, Korea.
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute , Cheongju 28119, Korea.|Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon 34141, Korea.
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Sookmyung Women's University , Seoul 04310, Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Chang
authors.affiliation: Department of Chemistry, Sookmyung Women's University , Seoul 04310, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute , Cheongju 28119, Korea.|Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon 34141, Korea.
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Hong
authors.affiliation: Department of Chemistry, Korea University , Seoul 02841, Korea.
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Chemistry, University of Texas at Austin , Austin, Texas 78712-1224, United States.
authors.forename: Jonathan L
authors.identifier: 0000-0002-9576-1325
authors.initials: JL
authors.lastname: Sessler
mesh_terms: D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D058972:Folic Acid Transporters / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*; D009362:Neoplasm Metastasis; D011166:Porphyrins / Q000737:chemistry*; D011355:Prodrugs / Q000378:metabolism; D000068936:Theranostic Nanomedicine / Q000379:methods*
chemical_list: D058972:Folic Acid Transporters; D008081:Liposomes; D011166:Porphyrins; D011355:Prodrugs; C442892:texaphyrin; D004317:Doxorubicin; D005978:Glutathione