State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 999078, Macau, China.
Institute of Functional Nano & Soft Materials Laboratory (FUNSOM), Soochow University, Suzhou, Jiangsu, 215123, China.
Adv Mater. 2017 Oct;29(40). doi: 10.1002/adma.201703588. Epub 2017 Aug 21.
Near-infrared (NIR)-light-triggered photothermal therapy (PTT) usually requires hyperthermia to >50 °C for effective tumor ablation, which can potentially induce inflammatory disease and heating damage of normal organs nearby, while tumor lesions without sufficient heating (e.g., the internal part) may survive after treatment. Achieving effective tumor killing under relatively low temperatures is thus critical toward successful clinical use of PTT. Herein, we design a simple strategy to fabricate poly(ethylene glycol) (PEG)-modified one-dimensional nanoscale coordination polymers (1D-NCPs) with intrinsic biodegradability, large surface area, pH-responsive behaviors, and versatile theranostic functions. With NCPs consisting of Mn2+/indocyanine green (ICG) as the example, Mn-ICG@pHis-PEG display efficient pH-responsive tumor retention after systemic administration and then load Gambogic acid (GA), a natural inhibitor of heat-shock protein 90 (Hsp90) that plays an essential role for cells to resist heating-induced damage. Such Mn-ICG@pHis-PEG/GA under a mild NIR-triggered heating is able to induce effective apoptosis of tumor cells, realizing low-temperature PTT (~43 °C) with excellent tumor destruction efficacy. This work not only develops a facile approach to fabricate PEGylated 1D-NCPs with tumor-specific pH responsiveness and theranostic functionalities, but also presents a unique low-temperature PTT strategy to kill cancer in a highly effective and minimally invasive manner.
近红外（NIR）光触发光热疗法（PTT）通常需要将温度升高到 >50°C 以实现有效的肿瘤消融，这可能会引起炎症性疾病和邻近正常器官的加热损伤，而肿瘤病变部位如果没有足够的加热（例如内部），在治疗后可能会存活下来。因此，实现在相对较低温度下的有效肿瘤杀伤对于 PTT 的成功临床应用至关重要。在这里，我们设计了一种简单的策略来制备具有内在可生物降解性、大表面积、pH 响应行为和多功能治疗学功能的聚乙二醇（PEG）修饰的一维纳米级配位聚合物（1D-NCPs）。以 NCPs 为例，由 Mn2+/吲哚菁绿（ICG）组成的 Mn-ICG@pHis-PEG 在系统给药后显示出高效的 pH 响应肿瘤保留，然后负载藤黄酸（GA），GA 是热休克蛋白 90（Hsp90）的天然抑制剂，在细胞抵抗加热诱导的损伤中起着至关重要的作用。在温和的 NIR 触发加热下，这种 Mn-ICG@pHis-PEG/GA 能够诱导肿瘤细胞有效凋亡，实现低温 PTT（~43°C），具有优异的肿瘤破坏效果。这项工作不仅开发了一种简便的方法来制备具有肿瘤特异性 pH 响应性和治疗功能的 PEG 化 1D-NCPs，而且还提出了一种独特的低温 PTT 策略，以高效、微创的方式杀死癌症。
