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一种有前景的锌(II)酞菁-喹啉共轭光敏剂的光动力抗癌活性增强及其机制

Improved photodynamic anticancer activity and mechanisms of a promising zinc(II) phthalocyanine-quinoline conjugate photosensitizer and .

作者信息

Chen Juanjuan, Wang Yingming, Fang Yuting, Jiang Zhihuan, Wang Aiping, Xue Jinping

机构信息

National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, and Fujian Engineering Research Center for Drug and Diagnoses-Treat of Photodynamic Therapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350116, China.

Hangzhou Zhizhong Pharmaceutical Technology Co., Ltd., Hangzhou, 310000, China.

出版信息

Biomed Opt Express. 2020 Jun 22;11(7):3900-3912. doi: 10.1364/BOE.394186. eCollection 2020 Jul 1.

Abstract

Since the discovery of photodynamic therapy, scientists have constantly been searching for more effective and ideal photosensitizers (PSs). As part of our ongoing interest in the development of more potent photosensitizers, quinoline-8-yloxy-substituted zinc(II) phthalocyanine () has been identified as a promising photosensitizers in tumor cells. This study aims to explore the photodynamic mechanism and photodynamic efficacy of , and further evaluate its potential in clinical photodynamic therapy application. The single crystal structure of enables the easy control of clinical quality standards. In comparison with Photofrin, exhibits considerably higher anticancer activity by dual dose-related mechanisms (antiproliferative and apoptosis). In addition, the results demonstrate that exhibits significant tumor regression with less skin photosensitivity by both direct killing and apoptosis anticancer mechanisms. In conclusion, can be considered to be a promising ideal PS for clinical application owing to its defined chemical structure without phthalocyanine isomerization, good absorption of tissue-penetrating red light, improved photodynamic therapy efficacy, and reduced skin phototoxicity.

摘要

自从发现光动力疗法以来,科学家们一直在不断寻找更有效、更理想的光敏剂(PSs)。作为我们对开发更高效光敏剂持续关注的一部分,喹啉 - 8 - 氧基取代的锌(II)酞菁()已被确定为肿瘤细胞中有前景的光敏剂。本研究旨在探索的光动力机制和光动力疗效,并进一步评估其在临床光动力治疗应用中的潜力。的单晶结构便于控制临床质量标准。与光卟啉相比,通过双重剂量相关机制(抗增殖和凋亡)表现出显著更高的抗癌活性。此外,结果表明,通过直接杀伤和凋亡抗癌机制,表现出显著的肿瘤消退且皮肤光敏性较低。总之,由于其明确的化学结构、无酞菁异构化、对组织穿透性红光的良好吸收、提高的光动力治疗疗效以及降低的皮肤光毒性,可被认为是临床应用中有前景的理想光敏剂。

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