Dual-path modulation of hydrogen peroxide to ameliorate hypoxia for enhancing photodynamic/starvation synergistic therapy,Journal of Materials Chemistry B

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Dual-path modulation of hydrogen peroxide to ameliorate hypoxia for enhancing photodynamic/starvation synergistic therapy
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-09-17 , DOI: 10.1039/d0tb01556c
Xinhe Liu _{1,

2,

3,

4,

5} , Jing Liu _{1,

2,

3,

4,

5} , Shangyu Chen _{4,

5,

6,

7,

8} , Yuxin Xie _{1,

2,

3,

4,

5} , Quli Fan _{4,

5,

6,

7,

8} , Jiahong Zhou _{3,

4,

5,

9} , Jianchun Bao _{1,

2,

3,

4,

5} , Tianxiang Wei _{1,

2,

3,

4,

5} , Zhihui Dai _{1,

2,

3,

4,

5}

Affiliation

The common existence of hypoxia within the tumor microenvironment severely restricts the efficacy of photodynamic therapy (PDT), which is attributed to the fact that the PDT process is strongly oxygen (O₂) dependent. Here, a multifunctional composite (named CPCG), which combines polyethylene glycol (PEG) functionalized cerium oxide nanoparticles (CeO₂) with photosensitizer chlorin e6 (Ce6) and glucose oxidase (GOx), is reported for generating O₂ within the tumor microenvironment by the dual-path hydrogen peroxide (H₂O₂)-modulated ways to ameliorate hypoxia, thereby enhancing the PDT efficiency. This process is realized based on the dual enzyme-like activity of CeO₂. The first modulated way is to transform the superoxide anion (O₂˙⁻) into H₂O₂ by the superoxide dismutase-like activity of CeO₂. The second modulated way is to decompose glucose into H₂O₂ through the catalysis of GOx. Subsequently, H₂O₂ generated from the above dual modulated ways can further produce O₂ via the catalase-like activity of CeO₂. Additionally, the depletion of glucose could impede the nutrient supply to obtain starvation therapy. Both in vitro and in vivo experiments indicate that the CPCG composite could enhance the efficacy of photodynamic/starvation synergistic therapy. Therefore, this strategy offers great potential to modulate the O₂ level in the tumor microenvironment for better therapeutic outcomes, and can act as a promising candidate in photodynamic/starvation synergistic therapy.

中文翻译：

双通路调节过氧化氢以改善缺氧，增强光动力/饥饿协同治疗

肿瘤微环境中常见的缺氧严重限制了光动力疗法（PDT）的功效，这归因于PDT过程强烈依赖氧气（O ₂）的事实。这里，多功能复合（名为CPCG），它结合了聚乙二醇（PEG）的官能化的氧化铈纳米颗粒（的CeO ₂）与光敏剂二氢卟酚e6（的Ce6）和葡萄糖氧化酶（GOx），报道用于产生Ò ₂由肿瘤微环境中通过双路径过氧化氢（H ₂ O ₂）调节的方式来改善缺氧，从而提高PDT效率。该过程是基于CeO ₂的双重酶样活性实现的。所述第一调制方式是变换超氧阴离子（O ₂ ˙ ^-）成H ₂ ö ₂通过的CeO的超氧化物歧化酶样活性₂。第二种调制方式是通过GOx催化将葡萄糖分解为H ₂ O ₂。接着，H ₂ ö ₂从上面的双重调制方式生成可进一步产生Ò ₂ 通过的CeO的过氧化氢酶样活性₂。另外，葡萄糖的消耗可能会阻碍营养供应，从而无法获得饥饿疗法。二者在体外和体内实验表明，CPCG复合材料可以增强光动力/饥饿协同治疗的功效。因此，该策略在调节肿瘤微环境中的O ₂水平以获得更好的治疗效果方面具有巨大潜力，并且可以作为光动力/饥饿协同治疗中的有希望的候选者。

更新日期：2020-10-11

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