Pharmacologic Vitamin C-Based Cell Therapy via Iron Oxide Nanoparticle-Induced Intracellular Fenton Reaction,ACS Applied Nano Materials

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Pharmacologic Vitamin C-Based Cell Therapy via Iron Oxide Nanoparticle-Induced Intracellular Fenton Reaction
ACS Applied Nano Materials ( IF 5.3 ) Pub Date : 2020-01-30 , DOI: 10.1021/acsanm.9b02405
Suman Pal ₁ , Nikhil R. Jana ₁

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Although the cytotoxic effect of iron oxide nanoparticle via peroxidase-like activity and associated Fenton reaction is well-known, its effective utilization in cancer therapy is limited because of poor availability of endogenous hydrogen peroxide. Similarly, the cytotoxic effect of vitamin C via hydrogen peroxide generation is well-known but its practical use in cancer therapy is limited due to requirement of high dose (typically above one milimolar) which is not achievable under physiological condition. Here, we show that pharmacologically achievable dose of vitamin C in the range of 0.1–1.0 mM can induce cell death via iron oxide nanoparticle-based intracellular Fenton reaction. Cells are exposed with exogenous vitamin C after labeling with Fe₃O₄ nanoparticle or directly exposing with vitamin C-conjugated Fe₃O₄ nanoparticle. Results show that intracellular Fe₃O₄ nanoparticle can induce cell death by as low as 0.1 mM exogenous vitamin C via Fenton reaction-based intracellular reactive oxygen species (ROS) generation. Following this approach, selective killing of cancer cell has been achieved via functional Fe₃O₄ nanoparticle-based cell targeting/labeling followed by exogenous vitamin C-based cell therapy. This approach can be extended for other nanoparticles with oxidase/peroxidase-like activity and in designing more effective nanoparticle for vitamin C-based cell therapy.

中文翻译：

氧化铁纳米粒子诱导的细胞内Fenton反应的药物基于维生素C的细胞治疗

尽管氧化铁纳米颗粒通过过氧化物酶样活性和相关的Fenton反应的细胞毒性作用是众所周知的，但由于内源性过氧化氢的利用率较差，其在癌症治疗中的有效利用受到限制。类似地，维生素C通过过氧化氢的产生的细胞毒性作用是众所周知的，但是由于需要在生理条件下无法达到的高剂量（通常高于一毫摩尔）而限制了其在癌症治疗中的实际应用。在这里，我们表明，药理学上可达到的剂量的维生素C在0.1–1.0 mM范围内可以通过基于氧化铁纳米颗粒的细胞内Fenton反应诱导细胞死亡。用Fe ₃ O ₄标记后，细胞暴露于外源性维生素C纳米颗粒或直接暴露于维生素C共轭的Fe ₃ O ₄纳米颗粒。结果表明，通过基于Fenton反应的细胞内活性氧（ROS）生成，细胞内Fe ₃ O ₄纳米颗粒可诱导低至0.1 mM外源维生素C的细胞死亡。按照这种方法，通过功能性的基于Fe ₃ O ₄纳米粒子的细胞靶向/标记，然后进行外源的基于维生素C的细胞疗法，已经实现了癌细胞的选择性杀伤。这种方法可以扩展到其他具有氧化酶/过氧化物酶样活性的纳米粒子，并可以设计出更有效的基于维生素C的细胞疗法纳米粒子。

更新日期：2020-01-31

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