title: Conjugation of 2-(1'-hexyloxyethyl)-2-devinylpyropheophorbide-a (HPPH) to carbohydrates changes its subcellular distribution and enhances photodynamic activity in vivo.
abstract: The carbohydrate moieties on conjugating with 3-(1'-hexyloxyethyl)-3-devinyl pyropeophorbide-a (HPPH) altered the uptake and intracellular localization from mitochondria to lysosomes. In vitro, HPPH-Gal 9 PDT showed increased PDT efficacy over HPPH-PDT as detectable by the oxidative cross-linking of nonphosphorylated STAT3 and cell killing in ABCG2-expressing RIF cells but not in ABCG2-negative Colon26 cells. This increased efficacy in RIF cells could at least partially be attributed to increased cellular accumulation of 9, suggesting a role of the ABCG2 transporter for which HPPH is a substrate. While such differences in the accumulation in HPPH derivatives by tumor tissue in vivo were not detectable, 9 still showed an elevated light dose-dependent activity compared to HPPH in mice bearing RIF as well as Colon26 tumors. Further optimization of the carbohydrate conjugates at variable treatment parameters in vivo is currently underway.
authors.affiliation: PDT Center, Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zheng
authors.forename: Janet
authors.initials: J
authors.lastname: Morgan
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Pandey
authors.forename: Yihui
authors.initials: Y
authors.lastname: Chen
authors.forename: Erin
authors.initials: E
authors.lastname: Tracy
authors.forename: Heinz
authors.initials: H
authors.lastname: Baumann
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Missert
authors.forename: Carrie
authors.initials: C
authors.lastname: Batt
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jackson
authors.forename: David A
authors.initials: DA
authors.lastname: Bellnier
authors.forename: Barbara W
authors.initials: BW
authors.lastname: Henderson
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Pandey
mesh_terms: D000818:Animals; D001692:Biological Transport; D002241:Carbohydrates / Q000737:chemistry*; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002986:Clinical Trials as Topic; D005690:Galactose / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism*; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D014018:Tissue Distribution
chemical_list: D002241:Carbohydrates; D017319:Photosensitizing Agents; D050796:STAT3 Transcription Factor; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D005690:Galactose