Free-Radical Cascade Generated by AIPH/Fe3O4-Coloaded Nanoparticles Enhances MRI-Guided Chemo/Thermodynamic Hypoxic Tumor Therapy
Free-Radical Cascade Generated by AIPH/Fe3O4-Coloaded Nanoparticles Enhances MRI-Guided Chemo/Thermodynamic Hypoxic Tumor Therapy
复制标题
AIPH/Fe3O4 共载纳米颗粒产生的自由基级联增强 MRI 引导化疗/热力学缺氧肿瘤治疗
DOI：
10.1021/acsami.2c05748
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Jinrong Peng
中科院分区：
文献类型：
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作者：
Wenting Li;Baoyuan Li;Bin Wu;Baocheng Tian;Xiangjun Chen;Changrong Wang;Wei Hong;Jinrong Peng
自由基，包括活性氧（ROS），在决定细胞的命运中起着关键作用。当自由基水平增加到致命值时，它会导致癌细胞衰老或细胞死亡。针对这种机制的策略提供了有希望的癌症治疗方法。然而，产生自由基的有效和可持续的系统，特别是不依赖氧的系统，仍然不足。在本文中，制备了有效地共同递送磁性纳米颗粒和2，2 ′-偶氮二[2-（2-咪唑啉-2-基）丙烷]-二盐酸盐（AIPH）的功能化的基于PLGA的纳米复合材料，以实现光热诱导的热力学疗法与巨噬细胞极化策略的组合;该疗法通过产生不依赖于氧的自由基级联来靶向缺氧肿瘤。这些杂化纳米颗粒可以在肿瘤微环境中积累，并且封装的MNP不仅用作增强磁共振成像的造影剂，而且还表现出预期的光热转换并触发AIPH分解以产生自由基，从而导致癌细胞死亡。更重要的是，来自凋亡或坏死癌细胞的细胞碎片携带非降解的MNP，其可以被募集的TAM内吞。MNP可以进一步诱导TAM转化为M1亚型，随后产生ROS。这项研究提供了一种替代方法，用于生成非氧依赖性自由基级联反应，用于磁共振成像PTT/TDT引导的肿瘤联合治疗。
Free radicals, including reactive oxygen species (ROS), play a critical role in determining cell’s fate. When the level of free radicals is increased to a fatal value, it causes cancer cells to undergo senescence or cell death. Strategies that target this mechanism offer promising therapies against cancer. However, efficient and sustainable systems that generate free radicals, especially oxygen-independent systems, remain deficient. Herein, functionalized PLGA-based nanocomposites that efficiently co-deliver magnetic nanoparticles and 2,2′-azobis[2-(2-imidazolin-2-yl) propane]-dihydrochloride (AIPH) were fabricated to achieve photothermal-induced thermodynamic therapy combined with macrophage polarization strategies; this therapy targets hypoxic tumors through the generation of an oxygen-independent free-radical cascade. These hybrid NPs can accumulate in the tumor microenvironment, and the encapsulated MNPs not only serve as contrast agents for enhanced magnetic resonance imaging but also exhibit the expected photothermal conversion and trigger the decomposition of AIPH to generate free radicals, thus causing cancer cell death. More importantly, the cell debris from apoptotic or necrotic cancer cells carries nondegraded MNPs, which can be endocytosed by recruited TAMs. MNPs can further induce TAMs to polarize to the M1 subtype to subsequently generate ROS. This study provides an alternative method for the generation of an oxygen-independent free-radical cascade for tumor co-therapy guided by magnetic resonance imaging PTT/TDT.