PDF(Pubmed)
Abstract：
Photodynamic therapy (PDT) relies on a series of photophysical and photochemical reactions leading to cell death. While effective for various cancers, PDT has been less successful in treating pigmented melanoma due to high light absorption by melanin. Here, this limitation is addressed by 2-photon excitation of the photosensitizer (2p-PDT) using ~100 fs pulses of near-infrared laser light. A critical role of melanin in enabling rather than hindering 2p-PDT is elucidated using pigmented and non-pigmented murine melanoma clonal cell lines in vitro. The photocytotoxicities were compared between a clinical photosensitizer (Visudyne) and a porphyrin dimer (Oxdime) with ~600-fold higher σ2p value. Unexpectedly, while the 1p-PDT responses are similar in both cell lines, 2p activation is much more effective in killing pigmented than non-pigmented cells, suggesting a dominant role of melanin 2p-PDT. The potential for clinical translational is demonstrated in a conjunctival melanoma model in vivo, where complete eradication of small tumors was achieved. This work elucidates the melanin contribution in multi-photon PDT enabling significant advancement of light-based treatments that have previously been considered unsuitable in pigmented tumors.
摘要：
光动力疗法(PDT)依赖于一系列导致细胞死亡的光物理和光化学反应。虽然对各种癌症有效，由于黑色素的高光吸收,PDT在治疗色素黑素瘤方面不太成功。这里,通过使用〜100fs近红外激光脉冲的光敏剂（2p-PDT）的双光子激发来解决此限制。使用色素和非色素鼠黑色素瘤克隆细胞系在体外阐明了黑色素在启用而不是阻碍2p-PDT中的关键作用。比较了临床光敏剂（Visudyne）和卟啉二聚体（Oxdime）之间的光细胞毒性，σ2p值高约600倍。出乎意料的是,虽然两种细胞系的1p-PDT反应相似，2p激活比非色素细胞更有效地杀死色素细胞，提示黑色素2p-PDT的主导作用。在体内结膜黑色素瘤模型中证明了临床转化的潜力，在那里实现了小肿瘤的完全根除。这项工作阐明了黑色素在多光子PDT中的贡献，从而使以前被认为不适合色素沉着肿瘤的基于光的治疗取得了重大进展。
