title: Elimination of primary tumours and control of metastasis with rationally designed bacteriochlorin photodynamic therapy regimens.
abstract: Photodynamic therapy (PDT) with current photosensitisers focuses on local effects and these are limited by light penetration in tissues. We employ a stable near-infrared (NIR) absorbing bacteriochlorin with ca. 8h plasma half-life to increase the depth of the treatment and elicit strong systemic (immune) responses. Primary tumour growth delays and cures of BALB/c and nude mice bearing CT26 mouse colon carcinoma are related to the parameters that control PDT efficacy. The systemic anti-tumour protection elicited by the optimised PDT regimen is assessed by tumour rechallenges and by resistance to the establishment of metastasis after intravenous injection of CT26 cells. The optimised treatment regime offered 86% cure rate in BALB/c mice but no cures in BALB/c nude mice. Cured mice rechallenged over 3 months later with CT26 cells rejected the tumour cells in 67% of the cases. PDT of a subcutaneous CT26 tumour 5days after the additional intravenous injection of CT26 cells very significantly reduced lung metastasis. The PDT regimen optimised for the bacteriochlorin leads to remarkable long-term survival rates, effective immune memory and control of lung metastasis.
authors.affiliation: Luzitin SA, R. Bayer, S. Martinho do Bispo, 3045-016 Coimbra, Portugal.
authors.forename: Luis B
authors.initials: LB
authors.lastname: Rocha
authors.affiliation: Chemistry Department, University of Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Lígia C
authors.initials: LC
authors.lastname: Gomes-da-Silva
authors.affiliation: Faculty of Chemistry, Jagiellonian University, 30-060 Kraków, Poland. Electronic address: jdabrows@chemia.uj.edu.pl.
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Dąbrowski
authors.affiliation: Luzitin SA, R. Bayer, S. Martinho do Bispo, 3045-016 Coimbra, Portugal; Chemistry Department, University of Coimbra, 3004-535 Coimbra, Portugal. Electronic address: lgarnaut@ci.uc.pt.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Arnaut
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D007156:Immunologic Memory; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D013997:Time Factors; D047368:Tumor Burden
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C452433:bacteriochlorin
keywords: Anti-cancer activity; Anti-tumour immunity; Bacteriochlorins; Cancer; Metastasis; Photodynamic therapy; Photodynamic-immunotherapy; Photosensitiser; Phototoxicity