In recent years, the emergence of non-toxic but catalytically active inorganic nanoparticles has attracted great attention for cancer treatment, but the therapeutic effect has been affected by the limited reactive oxygen species in tumors. Therefore, the combination of chemotherapy and chemodynamic therapy is regarded as a promising therapeutic strategy. In this paper, we reported the preparation and bioactivity evaluation of poly(lactic acid-co-glycolic acid) (PLGA) grafted-γ-Fe₂O₃ nanoparticles with dual response of endogenous peroxidase and catalase like activities. Our hypothesis is that PLGAgrafted γ-Fe₂O₃ nanoparticles could be used as a drug delivery system for the anti-tumor drug doxorubicin to inhibit the growth of lung adenocarcinoma A549 cells; meanwhile, based on its mimic enzyme properties, this kind of nanoparticles could be combined with doxorubicin in the treatment of A549 cells. Our experimental results showed that the PLGAgrafted γ-Fe₂O₃ nanoparticles could simulate the activity of catalase and decompose hydrogen peroxide into H₂O and oxygen in neutral tumor microenvironment, thus reducing the oxidative damage caused by hydrogenperoxide to lung adenocarcinoma A549 cells. In acidic microenvironment, PLGA grafted γ-Fe₂O₃ nanoparticles could simulate the activity of peroxidase and effectively catalyze the decomposition of hydrogen peroxide to generate highly toxic hydroxyl radicals, which could cause the death of A549 cells. Furthermore, the synergistic effect of peroxidase-like activity of PLGA-grafted γ-Fe₂O₃ nanoparticles and doxorubicin could accelerate the apoptosisand destruction of A549 cells, thus enhancing the antitumor effect of doxorubicin-loaded PLGA-grafted γ-Fe₂O₃ nanoparticles. Therefore, this study provides an effective nanoplatform based on dual inorganic biomimetic nanozymes for the treatment of lung cancer.

中文翻译：

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PLGA 接枝磁赤铁矿纳米晶体的双重酶样性能及其对人肺腺癌 A549 细胞的协同化学/化学动力学治疗。

近年来，无毒但具有催化活性的无机纳米粒子的出现在癌症治疗中引起了极大的关注，但治疗效果受到肿瘤中有限的活性氧的影响。因此，化疗联合化学动力学疗法被认为是一种很有前景的治疗策略。在本文中，我们报道了具有内源性过氧化物酶和过氧化氢酶样活性双重响应的聚（乳酸-共-乙醇酸）（PLGA）接枝-γ- Fe2O3纳米颗粒的制备和生物活性评价。我们的假设是 PLGAgrafted γ-Fe₂O₃纳米颗粒可作为抗肿瘤药物阿霉素的给药系统，抑制肺腺癌A549细胞的生长；同时，基于其模拟酶的特性，这种纳米颗粒可以与阿霉素联合治疗 A549 细胞。我们的实验结果表明，PLGAgrafted γ- Fe₂O₃纳米粒子可以模拟过氧化氢酶的活性，在中性肿瘤微环境中将过氧化氢分解为H2O和氧气，从而减少过氧化氢对肺腺癌A549细胞的氧化损伤。在酸性微环境中，PLGA接枝γ-Fe₂O₃纳米颗粒可以模拟过氧化物酶的活性，有效催化过氧化氢分解产生剧毒的羟基自由基，从而导致A549细胞死亡。此外，协同作用过氧化物酶样PLGA-接枝的活性γ -Fe₂O₃纳米颗粒和多柔比星可促进A549细胞的凋亡和破坏，从而提高负载阿霉素的PLGA-接枝的抗肿瘤效果γ -Fe₂O₃纳米颗粒。因此，本研究为基于双无机仿生纳米酶治疗肺癌提供了有效的纳米平台。