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基于聚多巴胺的多功能抗肿瘤纳米剂用于通过调节氧化还原平衡进行光疗和光诊断

Polydopamine-Based Multifunctional Antitumor Nanoagent for Phototherapy and Photodiagnosis by Regulating Redox Balance.

作者信息

Feng Jie, Gao Jia-Lin, Zhang Ruo-Yu, Ren Wen-Xiu, Dong Yu-Bin

机构信息

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, P. R. China.

出版信息

ACS Appl Bio Mater. 2020 Dec 21;3(12):8667-8675. doi: 10.1021/acsabm.0c01057. Epub 2020 Dec 6.

Abstract

The development of multifunctional nanoagents for the simultaneous achievement of high diagnostic and therapeutic performances is significant for precise cancer treatment. Herein, we report on a polydopamine (PDA)-based multifunctional nanoagent, , in which the methylene blue (MB) photosensitizer (PS) and l-arginine (l-Arg) tumor-targeting species are equipped. After selectively accumulating in tumor sites, glutathione (GSH)-responsive degradation can controllably release loaded MB to produce singlet oxygen (O) under near-infrared (NIR) photoirradiation. This GSH-depleted PS release process can not only weaken the body's antioxidant defence ability but also synergistically increase the O concentration. Therefore, GSH depletion-enhanced photodynamic therapy (PDT) efficiency is logically achieved by regulating the intracellular redox balance. In addition, our nanoagent can guide photoacoustic/NIR thermal dual-modal imaging and convert light into heat for cooperative cancer phototherapy because of the inherent photothermal conversion nature of PDA. As a result, excellent antitumor phototherapy (PDT + PTT) is achieved under the precise guidance of dual-modal imaging. This work not only realizes the integration of cancer diagnosis and treatment through PDA-based nanocarriers but also delivers dimensions in designing the next generation of multifunctional antitumor nanoagents for enhanced phototherapy and photodiagnosis by regulating the redox balance.

摘要

开发能够同时实现高诊断和治疗性能的多功能纳米制剂对于精确癌症治疗具有重要意义。在此,我们报道了一种基于聚多巴胺(PDA)的多功能纳米制剂,其中装载了亚甲蓝(MB)光敏剂(PS)和L-精氨酸(L-Arg)肿瘤靶向物质。在选择性地在肿瘤部位积累后,谷胱甘肽(GSH)响应性降解可可控地释放负载的MB,在近红外(NIR)光照射下产生单线态氧(O)。这种GSH消耗导致的PS释放过程不仅会削弱机体的抗氧化防御能力,还会协同增加O的浓度。因此,通过调节细胞内氧化还原平衡,逻辑上实现了GSH消耗增强的光动力疗法(PDT)效率。此外,由于PDA固有的光热转换特性,我们的纳米制剂可以引导光声/NIR热双模态成像,并将光转化为热用于协同癌症光疗。结果,在双模态成像的精确引导下实现了优异的抗肿瘤光疗(PDT + PTT)。这项工作不仅通过基于PDA的纳米载体实现了癌症诊断和治疗的整合,还为通过调节氧化还原平衡设计下一代用于增强光疗和光诊断的多功能抗肿瘤纳米制剂提供了思路。

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