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Nanozyme-catalyzed oxygen release from calcium peroxide nanoparticles for accelerated hypoxia relief and image-guided super-efficient photodynamic therapy.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-05-19 , DOI: 10.1039/d0bm00187b
Yuping Hu 1 , Xuechun Wang 1 , Peng Zhao 1 , Hao Wang 2 , Wei Gu 1 , Ling Ye 1
Affiliation  

Hypoxia within solid tumors severely limits the efficacy of photodynamic therapy (PDT). Biocompatible calcium peroxide nanoparticles (CaO2 NPs) have superior oxygen generating capacity for hypoxia relief but the relatively slow release of O2 from CaO2 NPs hampers the PDT efficacy enhancement. Herein, manganese dioxide (MnO2) is applied as a nanozyme to facilitate O2 release from CaO2 NPs. It is disclosed that the accelerated O2 release ensures a rapid and efficient amplification of the O2 level for an increased cytotoxic singlet oxygen production with chlorin e6 and leads to a down-regulated hypoxia-responsive protein expression, which eventually translates to a super-efficient PDT as evidenced by the complete eradication of mice bearing subcutaneous 4T1 tumors. Meanwhile, MnO2 imparts an MR T1 imaging modality for tumor detection and treatment planning. These findings signify the essential role of accelerated and efficient hypoxia relief in PDT efficacy enhancement and provide an effective paradigm to overcome hypoxia-associated resistance for an enhanced therapeutic efficacy.

中文翻译:

纳米酶催化的过氧化钙纳米颗粒中的氧释放可加速缺氧缓解和图像引导的超高效光动力疗法。

实体瘤内的缺氧严重限制了光动力疗法(PDT)的功效。具有生物相容性的过氧化钙纳米颗粒(CaO2 NP)具有出色的氧气生成能力,可缓解缺氧,但从CaO2 NP释放氧气的速度相对较慢,阻碍了PDT功效的增强。在此,二氧化锰(MnO2)被用作一种纳米酶,以促进O2从CaO2 NP中释放。据披露,加速的O2释放可确保快速有效地放大O2的水平,从而增加二氢卟酚e6产生的细胞毒单线态氧的产生,并导致缺氧反应蛋白的表达下调,最终转化为超高效的PDT完全消除带有皮下4T1肿瘤的小鼠即可证明。与此同时,MnO2为肿瘤检测和治疗计划赋予MR T1成像方式。这些发现表明加速和有效的缺氧缓解在PDT功效增强中的重要作用,并为克服缺氧相关的耐药性提供了有效的范例,从而增强了治疗功效。
更新日期:2020-03-30
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