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近红外染料共轭的氧化应激放大聚合物胶束用于双重成像和协同光热治疗。

Near infrared dye-conjugated oxidative stress amplifying polymer micelles for dual imaging and synergistic anticancer phototherapy.

机构信息

Department of BIN Convergence Technology, Chonbuk National University, Jeonju, Chonbuk, 561-756, Republic of Korea.

Department of Polymer Nano Science and Technology, Chonbuk National University, Jeonju, Chonbuk, 561-756, Republic of Korea.

出版信息

Biomaterials. 2018 Feb;154:48-59. doi: 10.1016/j.biomaterials.2017.10.043. Epub 2017 Oct 27.

DOI:10.1016/j.biomaterials.2017.10.043
PMID:29120818
Abstract

The recent advances in nanotechnology have led to the development of smart nanomaterials that combine diagnostic and therapeutic functions and provide synergistic anticancer effects through the combination of different treatment modalities. Here, we report a promising theranostic nanoconstruct that can translate into multiple functionalities: fluorescence/photoacoustic imaging, acid-triggered generation of ROS (reactive oxygen species), heat and singlet oxygen production under near infrared (NIR) laser irradiation, and coupling oxidative anticancer therapy to dual imaging-guided photothermal/photodynamic therapy. An NIR dye-conjugated hydroxyl radical generating biodegradable polymer (HRGP-IR) is employed as a theranostic nanoplatform. HRGP-IR could self-assemble to form micelles and elevate oxidative stress by generating hydrogen peroxide and hydroxyl radical. Under the NIR (808 nm) laser irradiation, HRGP-IR micelles also generate heat and singlet oxygen to induce cancer cell death. In mouse xenograft models, HRGP-IR micelles accumulated in tumors preferentially and the tumor could be detected by dual imaging. Effective tumor ablation was achieved by HRGP-IR micelles (5 mg/kg) combined with NIR laser irradiation, demonstrating the synergistic anticancer effects of oxidative stress with photothermal heating. Given their dual imaging capability, anticancer phototherapy and highly potent synergistic anticancer activity with NIR laser irradiation, HRGP-IR micelles hold great potential as a nanotheranostic agent for cancer treatment.

摘要

最近纳米技术的进展导致了智能纳米材料的发展,这些材料结合了诊断和治疗功能,并通过结合不同的治疗方式提供协同的抗癌效果。在这里,我们报告了一种有前途的治疗纳米结构,它可以转化为多种功能:荧光/光声成像、在近红外(NIR)激光照射下酸触发产生 ROS(活性氧)、热和单线态氧的产生,以及将氧化抗癌治疗与双成像引导光热/光动力治疗相结合。一种近红外染料偶联的羟基自由基产生可生物降解聚合物(HRGP-IR)被用作治疗纳米平台。HRGP-IR 可以自组装形成胶束,并通过产生过氧化氢和羟基自由基来提高氧化应激。在近红外(808nm)激光照射下,HRGP-IR 胶束还会产生热量和单线态氧,导致癌细胞死亡。在小鼠异种移植模型中,HRGP-IR 胶束优先聚集在肿瘤中,并且可以通过双成像检测到肿瘤。HRGP-IR 胶束(5mg/kg)与近红外激光照射相结合可实现有效的肿瘤消融,证明了氧化应激与光热加热的协同抗癌作用。鉴于其双重成像能力、抗癌光疗以及与近红外激光照射的高效协同抗癌活性,HRGP-IR 胶束有望成为癌症治疗的纳米治疗剂。

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