Department of Chemistry, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, IL, 60616, USA.
Department of Surgery, University of Illinois at Chicago, 1200 W Harrison St, Chicago, IL, 60607, USA.
Biochem Biophys Res Commun. 2022 Jan 22;589:254-259. doi: 10.1016/j.bbrc.2021.12.033. Epub 2021 Dec 15.
Indocyanine green (ICG) is an FDA-approved near infrared (NIR) imaging agent for diagnosis and imaging guided surgery. It also exhibits phototoxicity under high-dose NIR irradiation, expanding its application as a photo-therapeutic agent. Since ICG's efficiency as a type II photosensitizer has been controversial due to its low triplet state yield, other mechanisms have been explored. While claims of toxic decomposition products, accompanied by irreversible ICG photobleaching, were proposed as the main mechanism, evidences from systemic studies are lacking. In this work, we aimed to unravel the factors affecting ICG photobleaching and the associated photo-killing effect on neuroblastoma, one of the most common pediatric tumors but often escapes therapy. Specifically, we examined how albumin-induced ICG stabilization affects the ICG photobleaching process, and the effect of photobleached ICG on cell proliferation and viability of neuroblastoma cells. It was found that ICG photobleaching was significant only under aerobic conditions and was more efficient in solutions with higher concentration ICG monomers, which were stabilized from aggregates by the presence of BSA while increasing photobleaching and associated oxygen consumption. Photobleached ICG inhibited cell proliferation, indicating another effect of tumor treatment by ICG. Taken together, while enhanced photobleaching by BSA-bound ICG monomers may reduce the photodynamic effect targeting cellular components, the photoproducts directly contribute to tumor growth inhibition and assist in a secondary mechanism to stop tumor growth.
吲哚菁绿（ICG）是一种获得美国食品和药物管理局（FDA）批准的近红外（NIR）成像剂，可用于诊断和成像引导手术。它在高剂量 NIR 照射下也表现出光毒性，从而扩展了其作为光疗剂的应用。由于 ICG 的三重态产率低，作为 II 型光敏剂的效率一直存在争议，因此已经探索了其他机制。虽然提出了有毒分解产物的说法，同时伴随着不可逆的 ICG 光漂白，这被认为是主要机制，但缺乏系统研究的证据。在这项工作中，我们旨在揭示影响 ICG 光漂白的因素以及其对神经母细胞瘤（最常见的小儿肿瘤之一，但经常逃避治疗）的相关光杀伤作用。具体而言，我们检查了白蛋白诱导的 ICG 稳定如何影响 ICG 的光漂白过程，以及光漂白的 ICG 对神经母细胞瘤细胞增殖和活力的影响。结果发现，只有在有氧条件下 ICG 才会显著光漂白，并且在 ICG 单体浓度更高的溶液中效率更高，白蛋白的存在稳定了 ICG 单体，使其从聚集体中脱离，从而增加了光漂白和相关的耗氧量。光漂白的 ICG 抑制了细胞增殖，表明 ICG 对肿瘤的另一种治疗效果。总之，虽然 BSA 结合的 ICG 单体增强的光漂白可能会降低针对细胞成分的光动力效应，但光产物直接有助于肿瘤生长抑制，并有助于阻止肿瘤生长的二级机制。
