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自猝灭金属有机粒子作为光声成像引导的第二近红外窗口光化疗的双重模式治疗剂。

Self-Quenched Metal-Organic Particles as Dual-Mode Therapeutic Agents for Photoacoustic Imaging-Guided Second Near-Infrared Window Photochemotherapy.

机构信息

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province , Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou 350025 , P. R. China.

The Liver Center of Fujian Province , Fujian Medical University , Fuzhou 350025 , P. R. China.

出版信息

ACS Appl Mater Interfaces. 2018 Aug 1;10(30):25203-25212. doi: 10.1021/acsami.8b08419. Epub 2018 Jul 19.

Abstract

The nanosized metal-organic particles (NMOPs) recently have attracted tremendous attentions in biomedical applications. However, few studies have developed metal-organic nanoparticles (NMOPs) as near-infrared (NIR) II phototherapeutic agents and as Fenton-like agents for cancer theranostics. Herein, directly using organic dye and Cu(II)-ion complexes to construct NMOPs, as dual-mode therapeutic agent for PA imaging-guided photochemotherapy in NIR II window, is reported. The NMOPs are simply an assembly of Cu(II) ion and tetrahydroxyanthraquinone (THQ) complexes [Cu(II)-THQ] through the coordination effect, van der Waals force, and π-π interactions. After modification of polyethylene glycol (PEG-(NH)), the obtained Cu-THQNPs endow excellent biocompatibility and stability in physiological conditions. Because of the strong absorption at NIR II window and photoinduced electrontransfer (PET) mechanism, the Cu-THQNPs not only acted as an excellent photothermal agent with extremely high light-to-heat conversion ability (51.34%) at 1064 nm for phototherapy but also explored as the PA contrast agent for precisely tracking and guiding the therapy in vivo. Most strikingly, our Cu-THQNPs can be degraded by tumor-specific acidic-cleaving of the coordination bonds and follow by the slow release of Cu(II) into tumors, which can act as Fenton-like agents to generate OH from HO for enhancing the antitumor efficacy in vivo. With almost 100% prevention of the tumor growth for ca. 14 days and no obvious toxicity based on blood biochemical/histological analysis, this work highlights the Cu-THQNPs as an efficient NIR II therapeutic agent for precise cancer theranostics.

摘要

纳米尺寸的金属有机粒子(NMOPs)最近在生物医学应用中引起了极大的关注。然而,很少有研究将金属有机纳米粒子(NMOPs)开发为近红外(NIR)II 光热治疗剂和类芬顿试剂用于癌症治疗。在此,直接使用有机染料和 Cu(II)离子配合物构建 NMOPs,作为 NIR II 窗口中光化学治疗的 PA 成像引导的双模式治疗剂。NMOPs 通过配位作用、范德华力和π-π 相互作用简单地组装成 Cu(II)离子和四羟基蒽醌(THQ)配合物[Cu(II)-THQ]。经过聚乙二醇(PEG-(NH))修饰后,所得的 Cu-THQNPs 在生理条件下具有优异的生物相容性和稳定性。由于在 NIR II 窗口的强吸收和光诱导电子转移(PET)机制,Cu-THQNPs 不仅可以作为一种极好的光热剂,在 1064nm 处具有极高的光热转换能力(51.34%),用于光疗,还可以作为 PA 造影剂,在体内进行精确跟踪和指导治疗。最引人注目的是,我们的 Cu-THQNPs 可以通过肿瘤特异性的配位键酸裂解降解,并随后缓慢释放 Cu(II)进入肿瘤,从而可以作为类芬顿试剂,从 HO 中生成 OH 以增强体内的抗肿瘤疗效。由于近 100%的肿瘤生长得到预防,约 14 天,且基于血液生化/组织学分析无明显毒性,这项工作突出了 Cu-THQNPs 作为一种高效的 NIR II 治疗剂,用于精确的癌症治疗。

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