用于 MRI 引导的抗炎和抗肿瘤治疗的可切换 ROS 清除剂/发生器，具有增强的治疗效果和减少的副作用,Advanced Healthcare Materials

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用于 MRI 引导的抗炎和抗肿瘤治疗的可切换 ROS 清除剂/发生器，具有增强的治疗效果和减少的副作用
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2022-11-11 , DOI: 10.1002/adhm.202202043
Muyao Li ₁ , Linlin Huo ₁ , Jie Zeng ₁ , Guifen Zhu ₂ , Xiangqing Liu ₂ , Xianglong Zhu ₃ , Guoming Huang ₂ , Yi Wang ₁ , Kaiyuan Ni ₄ , Zhenghuan Zhao ₁

Affiliation

光动力疗法（PDT）中的光敏剂由于低选择性生物分布而在肿瘤和邻近正常组织中积累，导致不良副作用，限制了临床应用。在此，报道了一种智能纳米平台，它在正常组织中选择性地充当活性氧 (ROS) 清除剂，但在肿瘤微环境 (TME) 中充当 ROS 发生器，以在 PDT 期间差异控制肿瘤和周围正常组织中的 ROS 水平。通过下调 PDT 后正常组织中产生的具有抑制细胞因子波的 ROS，纳米平台降低了 PDT 中正常组织的炎症反应，最大限度地减少了 PDT 的副作用和肿瘤转移。或者，纳米平台通过 TME 中的谷胱甘肽 (GSH) 响应性降解从 ROS 清除剂切换到生成器，通过降低 GSH 水平和放大肿瘤中的氧化应激，有效提高 PDT 疗效。同时，释放的锰离子提供实时和原位的磁共振成像（MRI）信号变化，以监测催化活性的逆转过程，实现肿瘤的准确诊断。这种具有可激活 MRI 造影剂的 TME 响应性 ROS 清除剂/发生器可能为设计具有精确诊断、高疗效和低副作用的下一代 PDT 药物提供新的维度。

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Switchable ROS Scavenger/Generator for MRI-Guided Anti-Inflammation and Anti-Tumor Therapy with Enhanced Therapeutic Efficacy and Reduced Side Effects

Photosensitizer in photodynamic therapy (PDT) accumulates in both tumor and adjacent normal tissue due to low selective biodistribution, results in undesirable side effect with limited clinic application. Herein, an intelligent nanoplatform is reported that selectively acts as reactive oxygen species (ROS) scavenger in normal tissue but as ROS generator in tumor microenvironment (TME) to differentially control ROS level in tumor and surrounding normal tissue during PDT. By down-regulating the produced ROS with dampened cytokine wave in normal tissue after PDT, the nanoplatform reduces the inflammatory response of normal tissue in PDT, minimizing the side effect and tumor metastasis in PDT. Alternatively, the nanoplatform switches from ROS scavenger to generator through the glutathione (GSH) responsive degradation in TME, which effectively improves the PDT efficacy with reduced GSH level and amplified oxidative stress in tumor. Simultaneously, the released Mn ions provide real-time and in situ signal change of magnetic resonance imaging (MRI) to monitor the reversal process of catalysis activity and achieve accurate tumor diagnosis. This TME-responsive ROS scavenger/generator with activable MRI contrast may provide a new dimension for design of next-generation PDT agents with precise diagnosis, high therapeutic efficacy, and low side effect.

更新日期：2022-11-11

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