Gadolinium-Manganese-Based Nanoplatform Reverses Radiotherapy Resistant Factors for Radiotherapy Sensitization and Computed Tomography/Magnetic Resonance Dual-Modal Imaging

Yingwen Li, Panhong Niu, Zhenzhong Han, Xueqian Wang, Duanmin Gao, Yunjian Xu, Qingbin He, Jianfeng Qiu, Yinglun Sun
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Abstract

Insufficient reactive oxygen species originating from hypoxia and high glutathione (GSH) in the tumor microenvironment (TME) is an important reason for radiotherapy (RT) resistance. Currently, radiosensitizers that remodel TME are widely investigated to enhance RT. However, developing an effective nano-radiosensitization system that removes radiotherapy-resistant factors from TME to boost RT effect while visualizing tumor imaging to aid therapy remains a challenge. Herein, MnO2 nanosheets are grown on the surface of ultrasmall Eu-doped NaGdF4 (NaGdF4:Eu3+) nanoparticles and modified by biocompatible DSPE-PEG2000 to prepare NaGdF4:Eu3+@MnO2@PEG nanoparticles (denoted as GMP NPs) as a radiosensitizer, which not only can reverse the TME by degrading H2O2 to produce oxygen and consuming high GSH but also achieve computed tomography (CT)and magnetic resonance (MR) imaging. When GMP NPs synergize with X-ray, a better antitumor effect is achieved in both HeLa cells and tumor-bearing mice, compared with X-ray alone. In addition, both paramagnetic Mn2+ ionsproduced by decomposing MnO2 in TME and NaGdF4:Eu3+ nanoparticles enhance T1-weighted MR imaging. NaGdF4:Eu3+ nanoparticles containing high atomic number of Gd/Eu effectively attenuate X-ray to enhance CT imaging. The work provides new insights for developing an efficient RT sensitization platform integrating antitumor therapeutic effect as well as CT/MR dual-modal imaging.

Abstract Image

钆锰基纳米平台可逆转放疗抗性因素,用于放疗增敏和计算机断层扫描/磁共振双模态成像
肿瘤微环境(TME)中缺氧和高谷胱甘肽(GSH)导致的活性氧不足是放疗(RT)耐药的重要原因。目前,重塑肿瘤微环境的放射增敏剂被广泛用于增强放疗。然而,开发一种有效的纳米放射增敏系统,既能清除肿瘤微环境中的放疗耐药因子,提高放疗效果,又能通过可视化肿瘤成像辅助治疗,仍然是一项挑战。在此,MnO2 纳米片生长在超小 Eu 掺杂 NaGdF4(NaGdF4:Eu3+)纳米颗粒表面,并用生物相容性 DSPE-PEG2000 修饰,制备出 NaGdF4:Eu3+@MnO2@PEG 纳米粒子(简称 GMP NPs)作为放射增敏剂,不仅能通过降解 H2O2 产生氧气和消耗大量 GSH 来逆转 TME,还能实现计算机断层扫描(CT)和磁共振(MR)成像。当 GMP NPs 与 X 射线协同作用时,对 HeLa 细胞和肿瘤小鼠的抗肿瘤效果比单独使用 X 射线更好。此外,TME 中 MnO2 分解产生的顺磁 Mn2+ 离子和 NaGdF4:Eu3+ 纳米粒子都能增强 T1 加权磁共振成像。含有高原子序数 Gd/Eu 的 NaGdF4:Eu3+ 纳米粒子能有效衰减 X 射线,从而增强 CT 成像。这项工作为开发集抗肿瘤治疗效果和 CT/MR 双模态成像于一体的高效 RT 增敏平台提供了新的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
17.30
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