Pires Layla, Demidov Valentin, Wilson Brian C, Salvio Ana Gabriela, Moriyama Lilian, Bagnato Vanderlei S, Vitkin I Alex, Kurachi Cristina
São Carlos Institute of Physics, University of São Paulo, Sao Carlos-SP 13566-590, Brazil.
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Cancers (Basel). 2020 Jul 18;12(7):1956. doi: 10.3390/cancers12071956.
Treatment using light-activated photosensitizers (photodynamic therapy, PDT) has shown limited efficacy in pigmented melanoma, mainly due to the poor penetration of light in this tissue. Here, an optical clearing agent (OCA) was applied topically to a cutaneous melanoma model in mice shortly before PDT to increase the effective treatment depth by reducing the light scattering. This was used together with cellular and vascular-PDT, or a combination of both. The effect on tumor growth was measured by longitudinal ultrasound/photoacoustic imaging in vivo and by immunohistology after sacrifice. In a separate dorsal window chamber tumor model, angiographic optical coherence tomography (OCT) generated 3D tissue microvascular images, enabling direct in vivo assessment of treatment response. The optical clearing had minimal therapeutic effect on the in control, non-pigmented cutaneous melanomas but a statistically significant effect ( < 0.05) in pigmented lesions for both single- and dual-photosensitizer treatment regimes. The latter enabled full-depth eradication of tumor tissue, demonstrated by the absence of S100 and Ki67 immunostaining. These studies are the first to demonstrate complete melanoma response to PDT in an immunocompromised model in vivo, with quantitative assessment of tumor volume and thickness, confirmed by (immuno) histological analyses, and with non-pigmented melanomas used as controls to clarify the critical role of melanin in the PDT response. The results indicate the potential of OCA-enhanced PDT for the treatment of pigmented lesions, including melanoma.
使用光激活光敏剂进行治疗（光动力疗法，PDT）在色素性黑色素瘤中的疗效有限，主要原因是光在该组织中的穿透性较差。在此，在PDT前不久将一种光学清除剂（OCA）局部应用于小鼠皮肤黑色素瘤模型，以通过减少光散射来增加有效治疗深度。这与细胞和血管PDT或两者的组合一起使用。通过体内纵向超声/光声成像和处死后的免疫组织学来测量对肿瘤生长的影响。在一个单独的背窗室肿瘤模型中，血管造影光学相干断层扫描（OCT）生成三维组织微血管图像，从而能够直接在体内评估治疗反应。光学清除对对照的非色素性皮肤黑色素瘤的治疗效果最小，但在色素性病变中，对于单光敏剂和双光敏剂治疗方案均具有统计学显著效果（<0.05）。后者能够实现肿瘤组织的全层根除，这通过S100和Ki67免疫染色的缺失得以证明。这些研究首次在体内免疫受损模型中证明黑色素瘤对PDT有完全反应，并对肿瘤体积和厚度进行了定量评估，通过（免疫）组织学分析得到证实，且使用非色素性黑色素瘤作为对照以阐明黑色素在PDT反应中的关键作用。结果表明OCA增强型PDT在治疗包括黑色素瘤在内的色素性病变方面具有潜力。
