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Catalase-like metal–organic framework nanoparticles to enhance radiotherapy in hypoxic cancer and prevent cancer recurrence

机译:过氧化氢酶样金属-有机骨架纳米颗粒可增强缺氧性癌症的放射治疗并预防癌症复发

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摘要

Tumor hypoxia typically occurs inside a solid tumor with an inadequate oxygen supply, sharply reducing the therapeutic efficiency of radiotherapy and significantly increasing the risk of local tumor recurrence. Herein, we designed folic acid modified enzyme-like hafnium-based manganoporphyrin metal–organic framework nanoparticles (MnTCPP–Hf–FA MOF NPs) to overcome hypoxia-induced radioresistance and prevent postoperative recurrence. Hf, a high-Z element, can effectively absorb X-ray energy and convert O2 and H2O into reactive oxygen species to induce cell apoptosis. The MnTCPP ligand has an enzyme-like ability to catalytically decompose endogenous H2O2 into O2 for enhancing RT in hypoxic tumors. In vivo experiments revealed that the MOF NPs could effectively inhibit melanoma growth and prevent tumor postoperative recurrence with only one X-ray irradiation after intravenous injection. We expect that the current study provides a versatile approach for solving the critical radioresistance issue of hypoxic tumors.
机译:肿瘤缺氧通常发生在实体瘤内部,供氧不足,大大降低了放射治疗的治疗效率,并显着增加了局部肿瘤复发的风险。在这里,我们设计了叶酸修饰的类似酶的ha基锰卟啉金属-有机骨架纳米颗粒(MnTCPP-Hf-FA MOF NPs),以克服低氧引起的放射抵抗并防止术后复发。高Z元素Hf可以有效吸收X射线能量并将O2和H2O转化为活性氧,从而诱导细胞凋亡。 MnTCPP配体具有类似酶的能力,可将内源性H2O2催化分解为O2,以增强缺氧肿瘤的RT。体内实验表明,MOF NPs可以在静脉注射后仅进行一次X射线照射,从而有效抑制黑色素瘤的生长并防止肿瘤术后复发。我们希望当前的研究提供一种通用的方法来解决缺氧肿瘤的关键放射抵抗问题。

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