Peroxidase-Like Activity of Fe3O4@Carbon Nanoparticles Enhances Ascorbic Acid-Induced Oxidative Stress and Selective Damage to PC-3 Prostate Cancer Cells
Peroxidase-Like Activity of Fe3O4@Carbon Nanoparticles Enhances Ascorbic Acid-Induced Oxidative Stress and Selective Damage to PC-3 Prostate Cancer Cells
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Fe3O4@碳纳米颗粒的类过氧化物酶活性增强抗坏血酸诱导的氧化应激和对 PC-3 前列腺癌细胞的选择性损伤
DOI：
10.1021/am4042367
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发表时间：
2013-12-25
影响因子：
9.5
通讯作者：
Wang, Changchun
中科院分区：
文献类型：
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作者：
An, Qiao;Sun, Chuanyu;Wang, Changchun
抗坏血酸（AA）能够通过扰乱细胞的正常氧化还原状态，并通过产生大量活性氧物质（ROS）造成毒性作用来抑制癌细胞生长。然而，在可耐受剂量下抗坏血酸的临床应用受到体内相对较低疗效的困扰。本研究描述了一种用于抗坏血酸介导的治疗策略的类过氧化物酶复合纳米粒子的开发。基于一种高通量、一锅溶剂热方法，合成了Fe₃O₄@C纳米粒子（NPs），然后在其表面用叶酸（FA）进行修饰。特别关注在H₂O₂存在下通过显色反应对类过氧化物酶催化活性的评估。Fe₃O₄@C纳米粒子的碳壳包含部分石墨化的碳，从而促进了H₂O₂催化分解过程中的电子转移，导致产生高活性的羟基自由基。凭借磁响应性和受体结合特异性，Fe₃O₄@C - FA纳米粒子固有的类过氧化物酶催化活性显著促进了癌细胞中抗坏血酸诱导的氧化应激，并优化了外源性抗坏血酸的活性氧介导的抗肿瘤功效。使用人前列腺癌PC - 3细胞进行的体外实验表明，Fe₃O₄@C - FA纳米粒子作为一种过氧化物酶模拟物，从内源性H₂O₂产生羟基自由基，内源性H₂O₂是通过氧化应激过程响应外源性抗坏血酸而产生的。使用双试剂导致PC - 3细胞的细胞毒性增强，并且由于纳米粒子的协同作用，抗坏血酸的给药剂量显著降低。然而，由于正常细胞（HEK 293T细胞）似乎比癌细胞具有更高的应对额外产生的活性氧的能力，在这种情况下纳米粒子 - 抗坏血酸组合几乎没有造成损伤，证明由于活性氧在癌细胞中优先积累，可以实现对癌细胞的选择性杀伤。讨论了一种可能的活性氧介导的机制以阐明纳米粒子 - 抗坏血酸试剂的药物特性。总体而言，这项基础性研究揭示了类过氧化物酶纳米材料可用于调节氧化应激，通过产生高水平的内源性活性氧来选择性治疗癌细胞。
Ascorbic acid (AA) is capable of inhibiting cancer cell growth by perturbing the normal redox state of cells and causing toxic effects through the generation of abundant reactive-oxygen species (ROS). However, the clinical utility of AA at a tolerable dosage is plagued by a relatively low in vivo efficacy. This study describes the development of a peroxidase-like composite nanoparticle for use in an AA-mediated therapeutic strategy. On the basis of a high-throughput, one-pot solvothermal approach, Fe3O4@C nanoparticles (NPs) were synthesized and then modified with folic acid (FA). on the surface. Particular focus is concentrated on the assessment of peroxidase-like catalytic activity by a chromogenic reaction in the presence of H2O2. The carbon shell of Fe3O4@C NPs contains partially graphitized carbon and thus facilitates electron transfer in the catalytic decomposition of H2O2, leading to the production of highly reactive hydroxyl radicals. Along with magnetic responsiveness and receptor-binding specificity, the intrinsic peroxidase-like catalytic activity of Fe3O4@C-FA NPs pronouncedly promotes AA-induced oxidative stress in cancer cells and optimizes the ROS-mediated antineoplastic efficacy of exogenous AA. In vitro experiments using human prostate cancer PC-3 cells demonstrate that Fe3O4@C-FA NPs serve as a peroxidase mimic to create hydroxyl radicals from endogenous H2O2 that is yielded in response to exogenous AA via an oxidative stress process. The usage of a dual agent leads to the enhanced cytotoxicity of PC-3 cells, and, because of the synergistic effect of NPs, the administrated dosage of AA is reduced markedly. However, because normal cells (HEK 293T cells) appear to have a higher capacity to cope with additionally generated ROS than cancer cells, the NP-AA combination shows little damage in this case, proving that selective killing of cancer cells could be achieved owing to preferential accumulation of ROS in cancer cells. A possible ROS-mediated mechanism is discussed to elucidate the pharmaceutical profile of the NP-AA agent. In general, this foundational study reveals that the peroxidase-like nanomaterials are applicable for modulating oxidative stress for the selective treatment of cancer cells by generating a high level of endogenous ROS.