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氧化石墨烯负载钌(II)-聚乙二醇配合物用于溶酶体靶向成像及光动力/光热治疗

Graphene Oxide Decorated with Ru(II)-Polyethylene Glycol Complex for Lysosome-Targeted Imaging and Photodynamic/Photothermal Therapy.

机构信息

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University , Guangzhou 510275, PR China.

出版信息

ACS Appl Mater Interfaces. 2017 Mar 1;9(8):6761-6771. doi: 10.1021/acsami.6b13808. Epub 2017 Feb 14.

Abstract

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) can kill cancer cells more efficiently as compared with PTT or PDT treatment alone. In this work, we use nanohybrid rGO-Ru-PEG composed of reduced nanographene oxide (rGO) sheet and a phosphorescent polyethylene glycol modified Ru(II) complex (Ru-PEG) for combined PTT and PDT of cancer. Photosensitizer and imaging agent Ru-PEG is decorated onto delivery and PTT agent rGO via π-π stacking and hydrophobic interactions. The chemical structure and morphology have been characterized by various methods. The release of Ru-PEG from rGO surface is pH-dependent, and irradiation can increase the release rate considerably. The combined effects of PDT and PTT have been evaluated by cytotoxicity assay under serial irradiation at 808 nm (PTT) and 450 nm (PDT). Mechanism investigation shows that the nanohybrid can induce apoptosis through generation of reactive oxygen species (ROS) and cathepsin-initiated apoptotic signaling pathways under light excitation. rGO-Ru-PEG can be applied to in vivo photothermal imaging, and high treatment efficacy was achieved for in vivo antitumor experiments when irradiated with an 808 nm laser and a 450 nm laser. Our work provides an effective strategy for the construction of multifunctional imaging and phototherapeutic nanohybrids for the treatment of cancer.

摘要

与单独的光热疗法(PTT)或光动力疗法(PDT)相比,光热疗法(PTT)和光动力疗法(PDT)的联合治疗可以更有效地杀死癌细胞。在这项工作中,我们使用由还原氧化石墨烯(rGO)片和磷光聚乙二醇修饰的钌(II)配合物(Ru-PEG)组成的纳米杂化 rGO-Ru-PEG 来进行癌症的联合 PTT 和 PDT。光敏剂和成像剂 Ru-PEG 通过 π-π 堆积和疏水相互作用修饰在递送和 PTT 剂 rGO 上。通过各种方法对化学结构和形态进行了表征。Ru-PEG 从 rGO 表面的释放与 pH 值有关,并且照射可以大大增加释放速率。通过在 808nm(PTT)和 450nm(PDT)下进行连续照射的细胞毒性测定评估了 PDT 和 PTT 的联合作用。机制研究表明,纳米杂化物在光激发下通过生成活性氧(ROS)和组织蛋白酶引发的凋亡信号通路诱导细胞凋亡。rGO-Ru-PEG 可用于体内光热成像,并且在用 808nm 激光和 450nm 激光照射时,在体内抗肿瘤实验中实现了高治疗效果。我们的工作为构建用于癌症治疗的多功能成像和光热治疗纳米杂化物提供了一种有效的策略。

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