BiO_2–x Nanosheets as Radiosensitizers with Catalase-Like Activity for Hypoxia Alleviation and Enhancement of the Radiotherapy of Tumors

Abstract

Tumor hypoxia is known to be one of the vital factors that aggravate tumor resistance to radiation therapy (RT) in which oxygen plays a critical role in tumor destruction. Herein, we synthesize a simple nanoradiosensitizer based on ultrathin BiO2–x nanosheets (NSs) modified with Tween 20 (T-BiO2–x NSs) to overcome the hypoxia-induced radioresistance as well as increase the efficacy of RT. On the one hand, bismuth as a high-Z element can effectively enhance the sensitivity of RT by depositing a higher radiation dose in tumors. The semiconductor property also endows its photocatalytic ability to produce extra reactive oxygen species (ROS) by reaction with the surrounding water. On the other hand, the defect-abundant BiO2–x NSs are also found to decompose the highly expressed hydrogen peroxide (H2O2) at the tumor site into oxygen (O2) for combating hypoxia. Both in vitro and in vivo experiments indicate that the as-prepared T-BiO2–x NSs could effectively inhibit tumor growth with X-ray irradiation. Our work thus provides a simple nanoradiosensitizer with multifunctionalities for increasing the RT efficacy while alleviating tumor hypoxia at the same time.

Mechanisms of Reactive Oxygen Species Generated by Inorganic Nanomaterials for Cancer Therapeutics

“…Furthermore, defective inorganic radiosensitizers operate by nonexclusive mechanisms to enhance radiation effects on cancer cells. Zhao group reported defect-abundant BiO 2−x nanosheets (NSs) as radiosensitizers with catalase-like activity for hypoxia alleviation and tumor radiotherapy (Liu et al, 2020c). The oxygen defects in the BiO 2−x NSs function as traps for electrons, which are easily transferred to O 2 to form O 2…”

Applications of Nanozymes in Anti-Tumor Therapy

“…死，并且肿瘤细胞更易扩散和转移 [14] 。肿瘤细胞生长速度快，代谢迅速，对氧气和营养物质的需求 大，会造成肿瘤组织缺氧。而肿瘤微环境的酸性环境被认为主要是由于肿瘤细胞进行无氧代谢造成 的，在缺氧环境中大量的葡萄糖被分解，糖酵解产生大量乳酸而造成pH的下降。缺氧和酸性环境都 不适合正常细胞的生存，但这种异常的环境却意外地增强了肿瘤细胞的突变，进而加剧肿瘤细胞的 增殖。肿瘤细胞通过生长和增殖，更加加剧了肿瘤微环境的缺氧和酸性 [15] 。 [17,18] [12] 。此外，Pt@BP纳米材料通过调节缺氧环境，下调肿瘤坏死因子(HIF-1α)蛋白的表达，降低了治疗肿瘤的风险(图2)。结果表明，该材料能够有效缩小肿瘤体积，用于抗肿 瘤治疗。中科院谷战军研究员和国家纳米中心赵宇亮院士团队合成了一种过氧化氢酶活性的氧缺陷 BiO 2−x 纳米酶 [19] 。氧缺陷的构筑赋予了纳米酶过氧化氢酶活性，能够将肿瘤部位高表达的H 2 O 2 分解 为O 2 ，缓解肿瘤缺氧，并且下调HIF-1α的表达，增强放疗的治疗效果。近来，一种新型二维石墨炔 (GDY)稳定锚定CeO 2 纳米粒形成的GDY-CeO 2 纳米酶被合成 [20] ，该纳米酶表现出优越的过氧化物酶 活性，同样能够将H 2 O 2 分解为O 2 ，显著缓解肿瘤乏氧，并且可以诱导DNA损伤，实现肿瘤治疗。上 海交通大学程英升教授等人 [21]…”

Energy‐converting biomaterials for cancer therapy: Category, efficiency, and biosafety

“…The next‐generation magnetic‐converted H‐ECBs should feature the superior capability of heat generation, high specific absorption rate, and excellent dispersibility. Iron oxide nanoparticles (IONPs) have been considered as promising candidates for MHT due to their superior capability of heat generation upon external activation of the alternative magnetic field (AMF, Lak et al, 2018; Liu et al, 2020). The heating efficiency of magnetic biomaterials could be expressed by their specific absorption rate (SAR, Gandia et al, 2019; Pan, Li, et al, 2020).…”