用于肿瘤高效放射增敏的凋亡-铁死亡介导的活性氧物种放大器。

Reactive Oxygen Species Amplifier for Apoptosis-Ferroptosis Mediated High-Efficiency Radiosensitization of Tumors.

机构信息

Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P. R. China.

出版信息

ACS Nano. 2024 Apr 9;18(14):10288-10301. doi: 10.1021/acsnano.4c01625. Epub 2024 Apr 1.

Abstract

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.

摘要

ROS 产生不足和放射抵抗性一直是放射治疗(RT)失败的原因。开发一种能够激活 ROS 诱导的细胞凋亡和铁死亡的生物材料是增强 RT 敏感性的潜在策略。为了实现精确和高效的 RT,设计了具有双模成像、放大 ROS 生成和诱导细胞凋亡-铁死亡以敏化 RT 作用的治疗纳米平台 Au/Cu 纳米点(Au/CuNDs)。大量的 ROS 来源于三个方面:(1)当暴露于电离辐射时,Au/CuNDs 有效地吸收光子并发射各种电子,这些电子可以与水相互作用产生 ROS。(2)Au/CuNDs 作为一种类过氧化物酶,通过与肿瘤细胞中过表达的过氧化氢发生芬顿反应产生丰富的 ROS。(3)Au/CuNDs 耗尽过表达的谷胱甘肽,导致 ROS 积累。大量的 ROS 和电离辐射通过增加 DNA 损伤进一步导致细胞凋亡,并通过增强脂质过氧化作用导致铁死亡,显著提高了 RT 的治疗效率。此外,Au/CuNDs 作为一种优异的纳米探针,可用于肿瘤的高分辨率近红外荧光成像和计算机断层扫描。有前途的双模成像性能表明它们在临床癌症检测和成像引导的精确 RT 中具有潜在的应用,可在 RT 期间最小化对相邻正常组织的损伤。总之,我们开发的治疗纳米平台通过 ROS 激活的细胞凋亡-铁死亡实现了双模成像和 RT 敏化,为临床癌症诊断和治疗提供了有前途的前景。

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