Tumour-localizing and -photosensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP)

Fabris, Clara; Vicente, M. Graça H.; Hao, Erhong; Friso, Elisabetta; Borsetto, Lara; Jori, Giulio; Miotto, Giovanni; Colautti, P.; Moro, Davide; Esposito, J.; Ferretti, Alice; Róssi, Carlo; Nitti, Donato; Sotti, Guido; Soncin, Marina

doi:10.1016/j.jphotobiol.2007.09.012

Cited by 34 publications

(21 citation statements)

References 18 publications

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“…The majority of currently available data about PDT on human melanoma have been obtained from two-dimensional (2D) cultures of melanoma cell lines [50,58,59]. However, as we have previously mentioned, most of these studies failed to predict the efficiency of in vivo preclinical studies or clinical trials.…”

Section: Organotypic Human Skin ----mentioning

confidence: 99%

Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment

et al. 2015

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Melanoma is among the most aggressive and treatment-resistant human skin cancer. Photodynamic therapy (PDT), a minimally invasive therapeutic modality, is a promising approach to treating melanoma. It combines a non-toxic photoactivatable drug called photosensitizer with harmless visible light to generate reactive oxygen species which mediate the antitumor effects. The aim of this review was to compile the available data about PDT on melanoma. Our comparative analysis revealed a disconnection between several hypotheses generated by in vitro therapeutic studies and in vivo and clinical assays. This fact led us to highlight new preclinical experimental platforms that mimic the complexity of tumor biology. The tumor and its stromal microenvironment have a dynamic and reciprocal interaction that plays a critical role in tumor resistance, and these interactions can be exploited for novel therapeutic targets. In this sense, we review two strategies used by photodynamic researchers: (a) developing 3D culture systems which mimic tumor architecture and (b) heterotypic cultures that resemble tumor microenvironment to favor therapeutic regimen design. After this comprehensive review of the literature, we suggest that new complementary preclinical models are required to better optimize the clinical outcome of PDT on skin melanoma.

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Section: Organotypic Human Skin ----mentioning

confidence: 99%

Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment

et al. 2015

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“…23 It is worth noting that the maximum tumor:skin ratio determined for MNT in this work is 3-8 times higher than those reported for free photosensitizers in this murine melanoma model. [24][25][26] Based on these data demonstrating that tumor selectivity generally increases (Figure 3) while tumor accumulation rapidly decreases with time (dropping by more than 90% from 3 to 15 hours, see Supplementary data, Figure S4), we had chosen a time interval of 3 hours as a "happy medium" of significant tumor accumulation and selectivity rates for subsequent distribution and therapeutic experiments.…”

Section: In Vivo Targeting Evaluated With 125 I-labeled Mntmentioning

confidence: 99%

Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery

Slastnikova

Rosenkranz²,

Gulak³

et al. 2012

IJN

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Background: Modular nanotransporters (MNT) are recombinant multifunctional polypeptides created to exploit a cascade of cellular processes, initiated with membrane receptor recognition to deliver selective short-range and highly cytotoxic therapeutics to the cell nucleus. This research was designed for in vivo concept testing for this drug delivery platform using two modular nanotransporters, one targeted to the α-melanocyte-stimulating hormone (αMSH) receptor overexpressed on melanoma cells and the other to the epidermal growth factor (EGF) receptor overexpressed on several cancers, including glioblastoma, and head-and-neck and breast carcinoma cells. Methods: In vivo targeting of the modular nanotransporter was determined by immunofluorescence confocal laser scanning microscopy and by accumulation of 125 I-labeled modular nanotransporters. The in vivo therapeutic effects of the modular nanotransporters were assessed by photodynamic therapy studies, given that the cytotoxicity of photosensitizers is critically dependent on their delivery to the cell nucleus.Results: Immunohistochemical analyses of tumor and neighboring normal tissues of mice injected with multifunctional nanotransporters demonstrated preferential uptake in tumor tissue, particularly in cell nuclei. With 125 I-labeled MNT{αMSH}, optimal tumor:muscle and tumor:skin ratios of 8:1 and 9.8:1, respectively, were observed 3 hours after injection in B16-F1 melanoma-bearing mice. Treatment with bacteriochlorin p-MNT{αMSH} yielded 89%-98% tumor growth inhibition and a two-fold increase in survival for mice with B16-F1 and Cloudman S91 melanomas. Likewise, treatment of A431 human epidermoid carcinoma-bearing mice with chlorin e 6 -MNT{EGF} resulted in 94% tumor growth inhibition compared with free chlorin e 6 , with 75% of animals surviving at 3 months compared with 0% and 20% for untreated and free chlorin e 6 -treated groups, respectively. Conclusion:The multifunctional nanotransporter approach provides a new in vivo functional platform for drug development that could, in principle, be applicable to any combination of cell surface receptor and agent (photosensitizers, oligonucleotides, radionuclides) requiring nuclear delivery to achieve maximum effectiveness.

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“…A significant photosensitising efficiency was also observed for 41 and more than 95% cell mortality was observed upon irradiation with red light. Porphyrin 41 was also found to be accumulated by the tumor tissue of C57BL/6 mice bearing a subcutaneously transplanted melanotic melanoma 66 . The mice were subjected to a neutron source either after 0.5 h after intratumoral administration or at 24 h after intravenous injection.…”

Section: Fig 11mentioning

confidence: 95%

“…During this time period, 60 and 6 ppm of 10 B was found to be accumulated in the tumor tissues and irradiation of thermal neutrons delayed the growth of the tumor for 5-6 days 67 . Thus boron-loaded porphyrins like 41 could act as both PDT and BNCT agents and can be administered even to a very aggressive and radioresistant tumor such as melanotic melanoma 66,67 .…”

Section: Fig 11mentioning

confidence: 99%

New developments in the medicinal chemistry of carboranes

Satapathy

Dash

Maguire

et al. 2010

Collect. Czech. Chem. Commun.

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Tumour-localizing and -photosensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP)

Cited by 34 publications

References 18 publications

Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment

Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment

Modular nanotransporters: a multipurpose in vivo working platform for targeted drug delivery

New developments in the medicinal chemistry of carboranes

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