A long-lived cuprous bis-phenanthroline complex for the photodynamic therapy of cancer

Abstract Background: Photodynamic therapy (PDT) is an anticancer treatment that utilizes the interaction of light and a photosensitiser (PS), promoting tumour cell death mediated by generation of reactive oxygen species. In this study, we evaluated the in vitro photoactivity of four meso-substituted porphyrins and a porphyrin coupled to a fullerene. Methods: The cell line employed was the LM3 mammary adenocarcinoma, and the PS with the best photokilling activity was administered to mice bearing the LM3 subcutaneously implanted adenocarcinoma. The TEMCP4+ porphyrin and its analogue TEMCC4+ chlorine contain four identical carbazoyl substituents at the meso positions of the tetrapyrrolic macrocycle and have A4 symmetry. The TAPP derivative also has A4 symmetry, and it is substituted at the meso positions by aminopropoxy groups. The DAPP molecule has ABAB symmetry with aminopropoxy and the trifluoromethyl substituents in trans positions. The TCP-C604+ dyad is formed by a porphyrin unit covalently attached to the fullerene C60.Results: The PSs are taken up by the cells with the following efficiency: TAPP> TEMCP4+= TEMCC4+> DAPP >TCP-C604+, and the amount of intracellular PS correlates fairly with the photodamage degree, but also the quantum yields of singlet oxygen influence the PDT outcome. TAPP, DAPP, TEMCC4+ and TEMCP4+ exhibit high photoactivity against LM3 mammary carcinoma cells, being TAPP the most active. After topical application of TAPP on the skin of mice bearing LM3 tumours, the molecule is localized mainly in the stratum corneum, and at a lower extent in hair follicles and sebaceous glands. Systemic administration of TAPP produces a tumour: normal skin ratio of 31.4, and high accumulation in intestine and lung.Conclusion: The results suggest a potential use of topical TAPP for the treatment of actinic keratosis and skin adnexal neoplasms. In addition, selectivity for tumour tissue after systemic administration highlights the selectivity of and potentiality of TAPP as a new PS.

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Synthesis and photophysical properties of amphiphilic halogenated bacteriochlorins: new opportunities for photodynamic therapy of cancer

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424609000553 ◽

2009 ◽

Vol 13 (04n05) ◽

pp. 567-573 ◽

Cited By ~ 28

Author(s):

Mariette M. Pereira ◽

Carlos J.P. Monteiro ◽

Ana V.C. Simões ◽

Sara M.A. Pinto ◽

Luís G. Arnaut ◽

...

Keyword(s):

Photodynamic Therapy ◽

Photophysical Properties ◽

Synergetic Effect ◽

In Vitro Cytotoxicity ◽

Recent Contribution ◽

Photodynamic Therapy Of Cancer ◽

Promising Treatment ◽

Potential Use ◽

Effect Of Light

Photodynamic therapy (PDT) is a promising treatment for several types of cancers. It involves the synergetic effect of light, oxygen and an appropriate photosensitizer. Extensive studies on the synthetic modulation of the structure of tetrapyrrolic macrocycles allowed for the optimization of chemical and physical properties of such photosensitizers. The progress from porphyrins to chlorins and more recently to bacteriochlorins clearly shows the improvements achieved in PDT photosensitizers. This paper summarizes our recent contribution to the synthesis of stable amphiphilic halogenated meso-tetraarylbacteriochlorins. Their photophysics, in vitro cytotoxicity and phototoxicity are presented and their potential use as photosensitizer for PDT application is assessed.

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Novel meso-substituted porphyrin derivatives and its potential use in photodynamic therapy of cancer

BMC Cancer ◽

10.1186/s12885-021-08286-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Pablo Vallecorsa ◽

Gabriela Di Venosa ◽

M. Belén Ballatore ◽

Dario Ferreyra ◽

Leandro Mamone ◽

...

Keyword(s):

Photodynamic Therapy ◽

Normal Skin ◽

Hair Follicles ◽

Systemic Administration ◽

Mammary Adenocarcinoma ◽

Quantum Yields ◽

High Accumulation ◽

Photodynamic Therapy Of Cancer ◽

Potential Use

Abstract Background Photodynamic therapy (PDT) is an anticancer treatment that utilizes the interaction of light and a photosensitiser (PS), promoting tumour cell death mediated by generation of reactive oxygen species. In this study, we evaluated the in vitro photoactivity of four meso-substituted porphyrins and a porphyrin coupled to a fullerene. Methods The cell line employed was the LM3 mammary adenocarcinoma, and the PS with the best photokilling activity was administered to mice bearing the LM3 subcutaneously implanted adenocarcinoma. The TEMCP4+ porphyrin and its analogue TEMCC4+ chlorine contain four identical carbazoyl substituents at the meso positions of the tetrapyrrolic macrocycle and have A4 symmetry. The TAPP derivative also has A4 symmetry, and it is substituted at the meso positions by aminopropoxy groups. The DAPP molecule has ABAB symmetry with aminopropoxy and the trifluoromethyl substituents in trans positions. The TCP-C604+ dyad is formed by a porphyrin unit covalently attached to the fullerene C60. Results The PSs are taken up by the cells with the following efficiency: TAPP> TEMCP4+ = TEMCC4+ > DAPP >TCP-C604+, and the amount of intracellular PS correlates fairly with the photodamage degree, but also the quantum yields of singlet oxygen influence the PDT outcome. TAPP, DAPP, TEMCC4+ and TEMCP4+ exhibit high photoactivity against LM3 mammary carcinoma cells, being TAPP the most active. After topical application of TAPP on the skin of mice bearing LM3 tumours, the molecule is localized mainly in the stratum corneum, and at a lower extent in hair follicles and sebaceous glands. Systemic administration of TAPP produces a tumour: normal skin ratio of 31.4, and high accumulation in intestine and lung. Conclusion The results suggest a potential use of topical TAPP for the treatment of actinic keratosis and skin adnexal neoplasms. In addition, selectivity for tumour tissue after systemic administration highlights the selectivity of and potentiality of TAPP as a new PS.

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