Comparative Photodynamic Therapy of B16 Pigmented Melanoma with Different Generations of Sensitizers

Abstract

<jats:p> In order to apply photodynamic therapy to pigmented neoplasms, comparative photosensitizing studies of B 16 pigmented melanoma in C 57 B 1/6 mice were carried out with haematoporphyrin derivative (HpD), zinc(II) phthalocyanine ( ZnPc ), zinc(II) naphthalocyanine ( ZnNc ) and tetrabenzamido-substituted zinc(II) naphthalocyanine ( ZnNcA ). By injection of the optimal drug concentration and application of the optimal dose of light irradiation (the emission of the laser dye corresponding to the λ<jats:sub>max</jats:sub> value of the respective sensitizer) a phototherapeutic effect was observed only after photosensitization with the longest-wavelength-absorbing sensitizer, namely ZnNcA . It is supposed that the detected, through different assessment criteria, promising phototherapeutic effect after ZnNcA photosensitization of B 16 pigmented melanoma in mice is due to suitable structural, photophysical and photochemical properties of this sensitizer, but not due to a hyperthermic effect. This assumption is supported by the results obtained after irradiation of B 16 pigmented melanoma-bearing mice with the same fluence rate and fluence but without the sensitizer. In this case the tumour temperature did not increase by more than 35 °C and no changes in the mean tumour diameter or in the malignant subcellular components were detected. </jats:p>

Photodiagnosis and Photodynamic Therapy of Cutaneous Melanoma

“…These compounds could be used for photodiagnosis, as well for initiation of a photodynamic effect in the tumour cell, so that one could combine photodiagnosis with a subsequent photodynamic therapy of the lesion. Bearing in mind the specific optical properties of melanin, especially its strong absorption in the shorter wavelengths' spectral range, scientists have focused their efforts on the synthesis and study of long-wavelengths photosensitizers, such as phthalocyanines and naphthalocyanines, which absorb in the 670-760 nm range and fluoresce in the 680 -800 nm range Peeva et al, 1999;Shopova et al, 1999;Mantareva et al, 2005). The incident light must be of appropriate wavelength to ensure deep penetration in order to excite the native tissue chromophores of the malignant tissue.…”

“…These PSs have energy absorption band in the far red spectral region (> 660 nm) with high absorption coefficients which allows a deeper tissue penetration of the excitation light, enabling it to penetrate blood, melanin and fibrotic tissue. The studies in our laboratory on highly pigmented variety of malignant melanoma B16 demonstrated an effective diagnosis and PDT response by using phthalocyanine and naphthalocyanines metal complexes (MPcs and MNcs) with intensive far red absorption band (Michailov et al, 1997;Peeva et al, 1999;Mantareva et al, 1997;Woehrle et al, 1999). The competition for the absorption of melanin with the applied light decreases as a singleexponent when the wavelength is increased .…”

“…The treatment of pigmented melanomas with naphthalocyanines was successful. The phototoxicity studies performed with liposome-incorporated Zn(II)-phthalocyanine (Ciba-Geigy, Switzerland) and tetrabenzamido-substituted Zn(II)-naphthalocyanine, ZnPcA synthesized for PDT studies revealed a high PDT response (Peeva et al, 1999;Soncin et al, 1998).…”

Perspectives on the application of nanotechnology in photodynamic therapy for the treatment of melanoma

“…A series of modifications and improvements applied on classical PDT have led to better results for melanoma treatment. Studies with PS absorbing in the far-red region suggest that a high level of skin pigmentation is not an obstacle for applying PDT against pigmented tumors, such as B16 pigmented melanoma ( 61 , 62 ). However, as stated by Bechet and collaborators ( 32 ), the majority of existent PS have not yet made it to clinical trials due to factors such as poor selectivity in terms of target tissue and healthy tissue, low extinction coefficients, absorption spectra at relatively short wavelengths, and high accumulation rates in the skin.…”

Porphyrin and Phthalocyanine Photosensitizers as PDT Agents: A New Modality for the Treatment of Melanoma

“…Six days post-transplant, tumor diameters were between 3 and 4 mm, at this point PDT treatment was initiated. [78] Tumor infected mice were injected with the photosensitizers and irradiated 24 h after injection with wavelengths between 630-780 nm. Twenty one days after PDT treatment HpD and ZnPc treated mice showed no effect on the tumors.…”