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Biodistribution and Photodynamic Efficacy of a Water‐Soluble, Stable, Halogenated Bacteriochlorin against Melanoma
Author(s) -
Dąbrowski Janusz M.,
Urbanska Krystyna,
Arnaut Luis G.,
Pereira Mariette M.,
Abreu Artur R.,
Simões Sérgio,
Stochel Grażyna
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000524
Subject(s) - phototoxicity , biodistribution , photodynamic therapy , in vivo , melanoma , chemistry , toxicity , in vitro , pharmacokinetics , photosensitizer , pharmacology , cancer research , irradiation , biochemistry , medicine , photochemistry , biology , organic chemistry , physics , microbiology and biotechnology , nuclear physics
The in vitro phototoxicity of a photostable, synthetic, water‐soluble, halogenated bacteriochlorin, 5,10,15,20‐tetrakis(2‐chloro‐5‐sulfophenyl)bacteriochlorin (TCPBSO 3 H), toward mouse melanoma (S91) cells is ∼60‐fold higher than that of the analogous porphyrin, and is associated with very weak toxicity in the dark; 90 % of S91 cells were killed in response to a light dose of 0.26 J cm −2 in the presence of [TCPBSO 3 H]=5 μ M . In vivo toxicity toward DBA mice is very low, even at doses of 20 mg kg −1 . In vivo pharmacokinetics and biodistribution of TCPBSO 3 H were studied in DBA mice with S91 tumors; 24 h after intraperitoneal injection of 10 mg kg −1 , TCPBSO 3 H demonstrated preferential accumulation in S91 mouse melanoma, with tumor‐to‐normal tissue ratios of 3 and 5 for muscle and skin, respectively. Photodynamic therapy (PDT) performed under these conditions, with 90 mW cm −2 diode laser irradiation at λ 750 nm for 20 min (total light dose of 108 J cm −2 ), resulted in tumor regression. Tumor recurrence was observed only approximately two months after treatment, confirming the efficacy of this PDT against melanoma.