title: Highly Effective Dual-Function Near-Infrared (NIR) Photosensitizer for Fluorescence Imaging and Photodynamic Therapy (PDT) of Cancer.
abstract: We report herein the synthesis and biological efficacy of near-infrared (NIR), bacteriochlorin analogues: 3-(1'-butyloxy)ethyl-3-deacetyl-bacteriopurpurin-18-N-butylimide methyl ester (3) and the corresponding carboxylic acid 10. In in vitro assays, compared to its methyl ester analogue 3, the corresponding carboxylic acid derivative 10 showed higher photosensitizing efficacy. However, due to drastically different pharmacokinetics in vivo, the PS 3 (HPLC purity >99%) showed higher tumor uptake and long-term tumor cure than 10 (HPLC purity >96.5%) in BALB/c mice bearing Colon 26 tumors. Isomerically pure R- and S- isomers of 3 (3a and 3b, purity by HPLC > 99%) under similar treatment parameters showed identical efficacy in vitro and in vivo. In addition, photosensitizer (PS) 3 showed limited skin phototoxicity and provides an additional advantage over the clinically approved chemically complex hematoporphyrin derivative as well as other porphyrin-based PDT agents, which makes 3 a promising dual-function agent for fluorescence-guided surgery with an option of phototherapy of cancer.
authors.forename: Nayan
authors.initials: N
authors.lastname: Patel
authors.forename: Paula
authors.initials: P
authors.lastname: Pera
authors.forename: Penny
authors.initials: P
authors.lastname: Joshi
authors.forename: Mykhaylo
authors.initials: M
authors.lastname: Dukh
authors.forename: Walter A
authors.initials: WA
authors.lastname: Tabaczynski
authors.affiliation: Photolitec, LLC , 73 High Street, Buffalo, New York 14203, United States.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Siters
authors.affiliation: Photolitec, LLC , 73 High Street, Buffalo, New York 14203, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Kryman
authors.forename: Ravindra R
authors.initials: RR
authors.lastname: Cheruku
authors.forename: Farukh
authors.initials: F
authors.lastname: Durrani
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Missert
authors.forename: Ramona
authors.initials: R
authors.lastname: Watson
authors.affiliation: College of Optoelectronic Engineering, Shenzhen University , Shenzhen, Guangdong 518060, China.|Institute of Lasers, Photonics and Biophotonics, University of Buffalo , Buffalo, New York 14260, United States.
authors.forename: Tymish Y
authors.initials: TY
authors.lastname: Ohulchanskyy
authors.forename: Erin C
authors.initials: EC
authors.lastname: Tracy
authors.forename: Heinz
authors.initials: H
authors.lastname: Baumann
authors.affiliation: Photolitec, LLC , 73 High Street, Buffalo, New York 14203, United States.
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Pandey
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005453:Fluorescence; D007259:Infrared Rays; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; C452433:bacteriochlorin