Femtosecond pulsed laser photodynamic therapy activates melanin and eradicates malignant melanoma

• 成果类型: Article
• 署名作者: Pires, Layla; Khattak, Shireen; Pratavieira, Sebastiao; Calcada, Carla; Romano, Renan; Yucel, Yeni; Bagnato, Vanderlei S.; Kurachi, Cristina; Wilson, Brian C.
• 署名单位: University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; Universidade de Sao Paulo; University of Toronto; Saint Michaels Hospital Toronto; University of British Columbia; Texas A&M University System; Texas A&M University College Station; University of Toronto
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15401
• DOI: 10.1073/pnas.2316303121
• 发表日期: 2024-04-02
• 关键词: choroidal melanoma; 2-photon excitation; in-vitro; photosensitizers; nanoparticles; TRENDS

摘要

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 sigma 2p 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.