title: In vitro cellular uptake and dimerization of signal transducer and activator of transcription-3 (STAT3) identify the photosensitizing and imaging-potential of isomeric photosensitizers derived from chlorophyll-a and bacteriochlorophyll-a.
abstract: Among the photosensitizers investigated, both ring-D and ring-B reduced chlorins containing the m-iodobenzyloxyethyl group at position-3 and a carboxylic acid functionality at position-17(2) showed the highest uptake by tumor cells and light-dependent photoreaction that correlated with maximal tumor-imaging [positron emission tomography (PET) and fluorescence] and long-term photodynamic therapy (PDT) efficacy in BALB/c mice bearing Colon26 tumors. However, among the ring-D reduced compounds, the isomer containing the 1'-m-iobenzyloxyethyl group at position-3 was more effective than the corresponding 8-(1'-m-iodobenzyloxyethyl) derivative. All photosensitizers showed maximum uptake by tumor tissue 24 h after injection, and the tumors exposed with light at low fluence and fluence rates (128 J/cm(2), 14 mW/cm(2)) produced significantly enhanced tumor eradication than those exposed at higher fluence and fluence rate (135 J/cm(2), 75 mW/cm(2)). Interestingly, dose-dependent cellular uptake of the compounds and light-dependent STAT3 dimerization have emerged as sensitive rapid indicators for PDT efficacy in vitro and in vivo and could be used as in vitro/in vivo biomarkers for evaluating and optimizing the in vivo treatment parameters of the existing and new PDT candidates.
authors.affiliation: Department of Cell Stress Biology/PDT Center, Molecular Pharmacology and Cancer Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, United States.
authors.forename: Avinash
authors.initials: A
authors.lastname: Srivatsan
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Wang
authors.forename: Penny
authors.initials: P
authors.lastname: Joshi
authors.forename: Munawwar
authors.initials: M
authors.lastname: Sajjad
authors.forename: Yihui
authors.initials: Y
authors.lastname: Chen
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Krishnakumar
authors.initials: K
authors.lastname: Thankppan
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Missert
authors.forename: Erin
authors.initials: E
authors.lastname: Tracy
authors.forename: Janet
authors.initials: J
authors.lastname: Morgan
authors.forename: Nestor
authors.initials: N
authors.lastname: Rigual
authors.forename: Heinz
authors.initials: H
authors.lastname: Baumann
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Pandey
mesh_terms: D000818:Animals; D025541:Bacteriochlorophyll A / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077194:Chlorophyll A; D006801:Humans; D007457:Iodine Radioisotopes; D007536:Isomerism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049268:Positron-Emission Tomography; D055503:Protein Multimerization; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D025541:Bacteriochlorophyll A; D007457:Iodine Radioisotopes; D017319:Photosensitizing Agents; D019275:Radiopharmaceuticals; D050796:STAT3 Transcription Factor; D002734:Chlorophyll; D000077194:Chlorophyll A