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铂-二氧化钛肖特基结作为纳米声敏剂、葡萄糖清除剂和肿瘤微环境调节剂用于促进癌症治疗

Platinum-Titania Schottky Junction as Nanosonosensitizer, Glucose Scavenger, and Tumor Microenvironment-Modulator for Promoted Cancer Treatment.

作者信息

Zhao Yinmin, Liu Jiahui, He Mengting, Dong Qi, Zhang Lei, Xu Zhigang, Kang Yuejun, Xue Peng

机构信息

School of Materials and Energy, Southwest University, Chongqing 400715, China.

Cancer Center, Medical Research Institute, Southwest University, Chongqing 400716, China.

出版信息

ACS Nano. 2022 Aug 23;16(8):12118-12133. doi: 10.1021/acsnano.2c02540. Epub 2022 Jul 29.

DOI:10.1021/acsnano.2c02540
PMID:35904186
Abstract

To date, the construction of heterogeneous interfaces between sonosensitizers and other semiconductors or noble metals has aroused increasing attention, owing to an enhanced interface charge transfer, augmented spin-flip, and attenuated activation energy of oxygen. Here, a smart therapeutic nanoplatform is constructed by surface immobilization of glucose oxidase (GOx) onto a TiO@Pt Schottky junction. The sonodynamic therapy (SDT) and starvation therapy (ST) mediated by TiO@Pt/GOx (TPG) promote systemic tumor suppression upon hypoxia alleviation in tumor microenvironment. The band gap of TiO@Pt is outstandingly decreased to 2.9 eV, in contrast to that of pristine TiO. The energy structure optimization enables a more rapid generation of singlet oxygen (O) and hydroxyl radicals (OH) by TiO@Pt under ultrasound irradiation, resulting from an enhanced separation of hole-electron pair for redox utilization. The tumorous reactive oxygen species (ROS) accumulation and GOx-mediated glucose depletion facilitate oxidative damage and energy exhaustion of cancer cells, both of which can be tremendously amplified by Pt-catalyzed oxygen self-supply. Importantly, the combinatorial therapy triggers intense immunogenetic cell death, which favors a follow-up suppression of distant tumor and metastasis by evoking antitumor immunity. Collectively, this proof-of-concept paradigm provides an insightful strategy for highly efficient SDT/ST, which possesses good clinical potential for tackling cancer.

摘要

迄今为止,由于界面电荷转移增强、自旋翻转增加以及氧的活化能降低,声敏剂与其他半导体或贵金属之间异质界面的构建引起了越来越多的关注。在此,通过将葡萄糖氧化酶(GOx)表面固定在TiO@Pt肖特基结上构建了一种智能治疗纳米平台。由TiO@Pt/GOx(TPG)介导的声动力疗法(SDT)和饥饿疗法(ST)在缓解肿瘤微环境中的缺氧后促进全身肿瘤抑制。与原始TiO相比,TiO@Pt的带隙显著降低至2.9 eV。能量结构优化使得TiO@Pt在超声照射下能够更快速地产生单线态氧(O)和羟基自由基(OH),这是由于空穴 - 电子对的分离增强以用于氧化还原利用。肿瘤活性氧(ROS)积累和GOx介导的葡萄糖消耗促进癌细胞的氧化损伤和能量耗尽,这两者都可以通过Pt催化的氧自供应极大地放大。重要的是,联合疗法引发强烈的免疫原性细胞死亡,这有利于通过激发抗肿瘤免疫对远处肿瘤和转移进行后续抑制。总体而言,这种概念验证范式为高效的SDT/ST提供了一种有洞察力的策略,在治疗癌症方面具有良好的临床潜力。

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