Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Biomater Sci. 2021 Dec 21;10(1):189-201. doi: 10.1039/d1bm01482j.
A series of glutathione (GSH)-responsive polydopamine (PDA) nanoparticles (NPs) were prepared using a disulfide-linked dopamine dimer as starting material, of which the size could be tuned systematically by adjusting the amount of ammonia solution used. Molecules of a phthalocyanine (Pc)-based photosensitiser and an epidermal growth factor receptor (EGFR)-targeting peptide were then sequentially immobilised on the surface of the NPs through coupling with the surface functionalities of PDA. The immobilised Pc molecules in the resulting nanosystem were photodynamically inactive due to the strong self-quenching effect and the quenching by the PDA core. Upon exposure to GSH in phosphate-buffered saline or EGFR-positive cancer cells, namely A549 and A431 cells, the NPs were disassembled through cleavage of the disulfide linkages to release the Pc molecules, thereby restoring their fluorescence emission and singlet oxygen generation. The NPs with the smallest size ( 200 nm in diameter) exhibited the highest cellular uptake and high photocytotoxicity with IC values as low as 0.05 μM based on Pc. These NPs could also accumulate and be activated in the tumour of A431 tumour-bearing nude mice, lighting up the tumour with fluorescence over a period of 72 h and completely eradicating the tumour through laser irradiation for 10 min (675 nm, 20 J cm). The results suggest that these biodegradable and versatile PDA-based NPs can serve as a promising nanoplatform for fabrication of advanced photosensitisers for targeted photodynamic therapy.
一系列谷胱甘肽 (GSH) 响应型聚多巴胺 (PDA) 纳米粒子 (NPs) 是使用二硫键连接的多巴胺二聚体作为起始材料制备的，通过调整使用的氨水溶液的量可以系统地调节其尺寸。然后，通过与 PDA 的表面官能团偶联，将基于酞菁 (Pc) 的光敏剂和表皮生长因子受体 (EGFR) 靶向肽的分子依次固定在 NPs 的表面上。由于强自猝灭效应和 PDA 核的猝灭，固定在所得纳米系统中的 Pc 分子由于光动力失活。在磷酸盐缓冲盐水或 EGFR 阳性癌细胞（即 A549 和 A431 细胞）中暴露于 GSH 时，通过二硫键的断裂使 NPs 解体，从而释放出 Pc 分子，从而恢复其荧光发射和单线态氧生成。具有最小尺寸（直径为 200nm）的 NPs 表现出最高的细胞摄取率和高的光细胞毒性，基于 Pc 的 IC 值低至 0.05μM。这些 NPs 还可以在 A431 荷瘤裸鼠的肿瘤中积累和被激活，在 72 小时内通过荧光点亮肿瘤，并通过激光照射 10 分钟（675nm，20Jcm）完全消除肿瘤。结果表明，这些可生物降解的多功能 PDA 基 NPs 可用作制造用于靶向光动力疗法的先进光敏剂的有前途的纳米平台。
