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三效合一纳米酶用于膀胱癌的放射增敏

Three-in-One Nanozyme for Radiosensitization of Bladder Cancer.

机构信息

Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, 130033, People's Republic of China.

Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Oct 26;19:10873-10883. doi: 10.2147/IJN.S463242. eCollection 2024.

Abstract

PURPOSE

Bladder cancer is a common malignancy of the urinary system and the development of noninvasive therapeutic methods is imperative to avoid radical cystectomy, which results in a poor quality of life for patients.

METHODS

In this study, ultrasmall copper-palladium nanozymes decorated with cysteamine (CPC) nanoparticles (NPs) were synthesized to enhance the efficacy of radiotherapy (RT) in treating bladder cancer. CPC NPs react with intracellular overexpressed HO in the tumor microenvironment to produce large quantities of reactive oxygen species (ROS) and induce tumor cell apoptosis. Furthermore, the CPC nanozymes can generate ample oxygen within tumors by utilizing HO, addressing hypoxia conditions, and mitigating radioresistance. Additionally, CPC facilitates the oxidation of glutathione (GSH) into oxidized glutathione disulfide (GSSG), blocking the self-repair mechanisms of tumor cells post-treatment. Simultaneously, CPC enhances the ionization energy deposition effect on tumor cells.

RESULTS

The results demonstrate an increased level of ROS and an elevation in oxygen content at the tumor site. Importantly, tumor growth was restrained without apparent systemic toxicity during the combined treatment.

CONCLUSION

In summary, this study highlights the potential of CPC nanozyme-mediated radiotherapy as a promising avenue for the effective treatment of bladder cancer and demonstrates its potential for future clinical applications in the synergistic therapy of bladder cancer.

摘要

目的

膀胱癌是泌尿系统常见的恶性肿瘤,开发非侵入性治疗方法对于避免导致患者生活质量下降的根治性膀胱切除术至关重要。

方法

本研究合成了巯基化的载铜钯纳米酶(CPC)纳米颗粒来增强放射疗法(RT)治疗膀胱癌的疗效。CPC 纳米颗粒与肿瘤微环境中过表达的 HO 反应,产生大量的活性氧(ROS)并诱导肿瘤细胞凋亡。此外,CPC 纳米酶可以通过利用 HO 产生大量的氧气,解决肿瘤中的缺氧问题,并减轻放射抵抗性。此外,CPC 促进谷胱甘肽(GSH)氧化为氧化型谷胱甘肽二硫化物(GSSG),阻止肿瘤细胞治疗后的自我修复机制。同时,CPC 增强了对肿瘤细胞的电离能量沉积效应。

结果

结果表明 ROS 水平增加,肿瘤部位的氧含量升高。重要的是,联合治疗时没有明显的全身毒性,肿瘤生长受到抑制。

结论

综上所述,本研究强调了 CPC 纳米酶介导的放射疗法作为治疗膀胱癌的一种有前途的方法的潜力,并展示了其在膀胱癌协同治疗中的未来临床应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d35/11523926/ff6a8250f9d6/IJN_A_463242_O_SCHF0001g.jpg

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