Local photodynamic action of methylene blue favorably modulates the postinterventional vascular wound healing response

Abstract

Photodynamic therapy (PDT), the light activation of photosensitizers to produce free radicals, is known to inhibit experimental intimal hyperplasia (IH). However, its clinical application has been limited by the lack of a suitable approach and a clinically appropriate photosensitizer. The aim of this study was to determine the effectiveness of a clinical approach for PDT, while testing its ability to favorably modulate the vascular wound healing response. Methods: Rat carotid arteries were balloon-injured (BI), and for PDT, the arteries were irradiated with thermoneutral laser light (λ = 660 nm, 100 J/cm 2 ) after the photosensitizer methylene blue (MB) was delivered locally. Control rats included BI alone and MB after BI alone. Arteries were analyzed after 2 weeks with morphometric evaluation (n = 6) and in situ hybridization for versican and procollagen type I gene expression (digitized image pixel analyses, n = 3). Results: No IH developed in PDT-treated arteries (0 ± 0 mm 2 ; compared with BI, 0.192 ± 0.006 mm 2 ; P < .0001). The diameters remained unchanged (PDT, 0.95 ± 0.04 mm; BI, 0.94 ± 0.05 mm; uninjured artery, 0.91 ± 0.06 mm). Arterial injury resulted in an increase of versican and procollagen type I messenger RNA (mRNA) in the adventitia and neointima. In the repopulating cells of the adventitia after PDT, there was a significant decrease in versican mRNA (% of positive pixels per high-power field: PDT, 1.13% ± 0.39%; BI, 2.93% ± 0.61%; P < .02), but not in procollagen type I mRNA. Conclusion:The decrease of versican mRNA expression of repopulating cells after PDT reflects favorable healing on a molecular level. Site-specific delivery of MB, a clinically appropriate photosensitizer, followed by PDT represents a suitable method to promote favorable healing after balloon intervention and further supports its role for inhibiting postinterventional restenosis.

Synthesis and characterization of hyaluronic acid hydrogels crosslinked using a solvent-free process for potential biomedical applications

“…Several papers can be found in the literature describing its use in photodynamic therapy in wound healing ( Heckenkamp, Adili, Kishimoto, Koch, & LaMuraglia, 2000 ; Sperandio, Simões, Corrêa Aranha, Corrêa, & Machado de Sousa, 2010 ). The light activation of photosensitizers, such as MB, produces reactive oxygen species and free radicals that could potentially inhibit experimental intimal hyperplasia ( Heckenkamp et al, 2000 ). Due to the transparency of the hydrogels described in the present work ( Fig.…”

Efeitos da terapia fotodinâmica e de uma única aplicação de laser de baixa potência em bactérias in vitro

“…A ausência de efeito bactericida no grupo tratado com TFD pode dever-se à concentração extremamente baixa do agente fotossensibilizante utilizado. O azul de metileno foi usado com essa finalidade devido a sua eficácia demonstrada em sensibilizar tais bactérias; além disso, apresenta absorção máxima de energia nas faixas próximas à do laser utilizado (>620 nm) 18 . Chan e Lai 25 relatam ter obtido efeitos bactericidas com concentrações dez vezes menores que a usada nesta pesquisa (0,1 µg/ml), porém Teichert et al 16 afirmam que a concentração ótima desse fotossensibilizante é de 500 mg/ml.…”

“…Tal técnica consiste na administração de um corante (fotossensibilizante) com posterior aplicação de radiação laser. O poder bactericida da TFD pode ser explicado pela escassa atenuação do laser em virtude da otimização da absorção gerada pelo corante, bem como pela produção de radicais livres (citotóxicos) pelo próprio corante, causando lesão na parede bacteriana [16][17][18] . O aumento da resistência das bactérias às drogas antibióticas gera a necessidade de desenvolver novos meios bacteriostáticos e bactericidas que colaborem com a terapêutica de indivíduos infectados.…”

Arterial wall strength after endovascular photodynamic therapy

“…In a chicken microvascular in vivo model it was also found that ALA based PDT led to an increased deposition of collagens in the arterial wall [27,28]. Furthermore, experiments in rats with methylene blue based PDT showed post treatment a significant increase of the amount of procollagen type I in the vascular wall, which may strengthen the blood vessel wall [29].…”