Theralase Inc, Toronto, ON, Canada.
Department of Chemistry, Acadia University, Wolfville, NS, Canada.
Photochem Photobiol. 2017 Oct;93(5):1248-1258. doi: 10.1111/php.12767. Epub 2017 Jun 13.
Cancer remains a major global malaise requiring the advent of new, efficient and low-cost treatments. Photodynamic therapy, which combines a photosensitizer and photons to produce cytotoxic reactive oxygen species, has been established as an effective cancer treatment but has yet to become mainstream. One of the main limitations has been the paucity of photosensitizers that are effective over a wide range of wavelengths, can exert their cytotoxic effects in hypoxia, are easily synthesized and produce few if any side effects. To address these shortfalls, three new osmium-based photosensitizers (TLD1822, TLD1824 and TLD1829) were synthesized and their photophysical and photobiological attributes determined. These photosensitizers are panchromatic (i.e. black absorbers), activatable from 200 to 900 nm and have strong resistance to photobleaching. In vitro studies show photodynamic therapy efficacy with both red and near-infrared light in normoxic and hypoxic conditions, which translated to good in vivo efficacy of TLD1829 in a subcutaneous murine colon cancer model.
癌症仍然是一个全球性的主要难题，需要新的、高效和低成本的治疗方法。光动力疗法结合了光敏剂和光子，产生细胞毒性的活性氧物质，已被确立为一种有效的癌症治疗方法，但尚未成为主流。主要限制之一是缺乏在广泛波长范围内有效的光敏剂，能够在缺氧环境中发挥其细胞毒性作用，易于合成，并且产生的副作用很少。为了解决这些不足，合成了三种新的基于锇的光敏剂（TLD1822、TLD1824 和 TLD1829），并确定了它们的光物理和光生物学特性。这些光敏剂是全色的（即黑色吸收剂），可在 200 至 900nm 范围内激活，并且具有很强的抗光漂白性。体外研究表明，在常氧和缺氧条件下，红色和近红外光都具有光动力治疗效果，这转化为 TLD1829 在皮下结肠癌细胞模型中的良好体内疗效。
