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Foscan and Foslip based photodynamic therapy in osteosarcoma in vitro and in intratibial mouse models


Meier, Daniela; Botter, Sander M; Campanile, Carmen; Robl, Bernhard; Gräfe, Susanna; Pellegrini, Giovanni; Born, Walter; Fuchs, Bruno (2017). Foscan and Foslip based photodynamic therapy in osteosarcoma in vitro and in intratibial mouse models. International Journal of Cancer, 140(7):1680-1692.

Abstract

Current osteosarcoma therapies cause severe treatment-related side effects and chemoresistance, and have low success rates. Consequently, alternative treatment options are urgently needed. Photodynamic therapy (PDT) is a minimally invasive, local therapy with proven clinical efficacy for a variety of tumor types. PDT is cytotoxic, provokes anti-vascular effects and stimulates tumor cell targeting mechanisms of the immune system and, consequently, has potential as a novel therapy for osteosarcoma patients. This study investigated the uptake and the dark- and phototoxicity and cytotoxic mechanisms of the photosensitizer (PS) 5,10,15,20-tetrakis(meta-hydroxyphenyl) chlorine (mTHPC, Foscan) and a liposomal mTHPC formulation (Foslip) in the human 143B and a mouse K7M2-derived osteosaroma cell line (K7M2L2) in vitro. Secondly the tumor- and metastasis-suppressive efficacies of mTHPC formulations based PDT and associated mechanisms in intratibial, metastasizing osteosarcoma mouse models (143B/SCID and syngeneic K7M2L2/BALB/c) were studied. The uptake of Foscan and Foslip in vitro was time- and dose-dependent and resulted in mTHPC and light dose-dependent phototoxicity associated with apoptosis. In vivo, the uptake of both i.v. administered mTHPC formulations was higher in tumor than in healthy control tissue. PDT caused significant (Foscan P<0.05, Foslip P<0.001) tumor growth inhibition in both models. A significant (Foscan P<0.001, Foslip P<0.001) immunsystem-dependent suppression of lung metastasis was only observed in the K7M2L2/BALB/c model and was associated with a marked infiltration of T-lymphocytes at the primary tumor site. This article is protected by copyright. All rights reserved.

Abstract

Current osteosarcoma therapies cause severe treatment-related side effects and chemoresistance, and have low success rates. Consequently, alternative treatment options are urgently needed. Photodynamic therapy (PDT) is a minimally invasive, local therapy with proven clinical efficacy for a variety of tumor types. PDT is cytotoxic, provokes anti-vascular effects and stimulates tumor cell targeting mechanisms of the immune system and, consequently, has potential as a novel therapy for osteosarcoma patients. This study investigated the uptake and the dark- and phototoxicity and cytotoxic mechanisms of the photosensitizer (PS) 5,10,15,20-tetrakis(meta-hydroxyphenyl) chlorine (mTHPC, Foscan) and a liposomal mTHPC formulation (Foslip) in the human 143B and a mouse K7M2-derived osteosaroma cell line (K7M2L2) in vitro. Secondly the tumor- and metastasis-suppressive efficacies of mTHPC formulations based PDT and associated mechanisms in intratibial, metastasizing osteosarcoma mouse models (143B/SCID and syngeneic K7M2L2/BALB/c) were studied. The uptake of Foscan and Foslip in vitro was time- and dose-dependent and resulted in mTHPC and light dose-dependent phototoxicity associated with apoptosis. In vivo, the uptake of both i.v. administered mTHPC formulations was higher in tumor than in healthy control tissue. PDT caused significant (Foscan P<0.05, Foslip P<0.001) tumor growth inhibition in both models. A significant (Foscan P<0.001, Foslip P<0.001) immunsystem-dependent suppression of lung metastasis was only observed in the K7M2L2/BALB/c model and was associated with a marked infiltration of T-lymphocytes at the primary tumor site. This article is protected by copyright. All rights reserved.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Pathology
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:osteosarcoma, photodynamic therapy, Foslip, Foscan, metastasis
Language:English
Date:2017
Deposited On:15 Feb 2017 12:47
Last Modified:21 Feb 2017 02:05
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0020-7136
Additional Information:This is the peer reviewed version of the following article: Meier, D., Botter, S. M., Campanile, C., Robl, B., Gräfe, S., Pellegrini, G., Born, W. and Fuchs, B. (2016), Foscan and Foslip based photodynamic therapy in osteosarcoma in vitro and in intratibial mouse models. Int. J. Cancer. Accepted Author Manuscript. doi:10.1002/ijc.30572, which has been published in final form at https://dx.doi.org/10.1002/ijc.30572. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-820227.html#terms).
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/ijc.30572
PubMed ID:27943293

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