3-Bromopyruvate-Loaded Ti3C2 MXene/Cu2O Nanosheets for Photoacoustic Imaging-Guided and Hypoxia-Relieving Enhanced Photothermal/Chemodynamic Therapy,Analytical Chemistry

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3-Bromopyruvate-Loaded Ti3C2 MXene/Cu2O Nanosheets for Photoacoustic Imaging-Guided and Hypoxia-Relieving Enhanced Photothermal/Chemodynamic Therapy
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-01-04 , DOI: 10.1021/acs.analchem.2c04953
Zichen Wang _{1,

2,

3} , Haimei Li ₄ , Wenyan She ₁ , Xiaoyang Zhang ₁ , Yang Liu ₁ , Yi Liu _{1,

4,

5} , Peng Jiang _{1,

2,

3,

6}

Affiliation

Chemodynamic therapy (CDT) is an innovative and effective treatment that relies on the Fenton or Fenton-like reaction, in which endogenous H₂O₂ overproduction is converted into cytotoxic hydroxyl radicals (^•OH) to suppress tumor growth. Nevertheless, the therapeutic efficiency of CDT is severely restricted by undesirable properties, such as reaction conditions and catalyst performance. Herein, a 2D Ti₃C₂ MXene/Cu₂O nanosheet (MCP NS)-based multifunctional nanoplatform (3-BP@MCG NSs) has been constructed, in which glucose oxidase (GOx) and respiration inhibitor 3-bromopyruvate (3-BP) are sequentially embedded. In this structure, the copper-based catalyst Cu₂O releases Cu⁺ in an acid-triggered manner in the tumor microenvironment (TME), which activates the Fenton-like reaction to catalyze the generation of ^•OH for CDT. The composite has excellent photothermal properties and a high-resolution photoacoustic imaging (PAI) capability in the near-infrared (NIR) region, and especially under NIR irradiation, the photothermal effect generated by the nanosheets accelerates catalysis. GOx is a natural enzyme catalyst for depleting glucose and oxygen content in cells, upregulating H₂O₂ levels in situ, and thereby improving the therapeutic effect of CDT. What is more, the supported 3-BP not only reduces oxygen consumption to alleviate hypoxia levels but also inhibits the glycolysis process and lowers ATP levels by suppressing hexokinase activity. As a result, 3-BP@MCG NSs optimize the unique properties of MCP NSs, GOx, and 3-BP via mutual promotion, realizing self-enhanced PTT/CDT synergistic therapy. This work establishes an emerging strategy for highly efficient PAI-guided integrated treatment and provides a proof of concept for the cooperation of hypoxia relief and in situ H₂O₂ and NIR synergistic enhancement to improve therapeutic efficiency.

中文翻译：

负载 3-溴丙酮酸的 Ti3C2 MXene/Cu2O 纳米片用于光声成像引导和缺氧缓解增强型光热/化学动力学治疗

化学动力学疗法 (CDT) 是一种创新且有效的治疗方法，它依赖于 Fenton 或 Fenton 样反应，其中内源性 H ₂ O ₂过量产生被转化为细胞毒性羟基自由基 ( ^• OH) 以抑制肿瘤生长。然而，CDT 的治疗效率受到反应条件和催化剂性能等不良特性的严重限制。在此，构建了基于二维 Ti 3 C 2 MXene/Cu 2 O 纳米片 (MCP NS) 的多功能纳米平台 (3-BP@MCG NSs)，其中葡萄糖氧化酶 (GOx) 和呼吸抑制剂_3-溴_丙酮酸( _3- BP）依次嵌入。在该结构中，铜基催化剂Cu ₂O 在肿瘤微环境 (TME) 中以酸触发的方式释放 Cu ⁺，从而激活类芬顿反应以催化CDT的^{• OH 生成。}该复合材料在近红外（NIR）区域具有优异的光热性能和高分辨率光声成像（PAI）能力，特别是在NIR照射下，纳米片产生的光热效应加速了催化作用。GOx 是一种天然酶催化剂，用于消耗细胞中的葡萄糖和氧气含量，原位上调 H ₂ O ₂水平，从而提高CDT的治疗效果。更重要的是，支持的 3-BP 不仅可以减少耗氧量以缓解缺氧水平，还可以通过抑制己糖激酶活性来抑制糖酵解过程并降低 ATP 水平。因此，3-BP@MCG NSs 通过相互促进优化了 MCP NSs、GOx 和 3-BP 的独特性质，实现了自我增强的 PTT/CDT 协同治疗。这项工作建立了一种高效的 PAI 指导综合治疗的新兴策略，并为缺氧缓解和原位H ₂ O ₂与 NIR 协同增强的合作以提高治疗效率提供了概念证明。

更新日期：2023-01-04

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