Wang Yang, Li Xun, Fang Yuan, Wang Jianhua, Yan Danhong, Chang Baisong
Department of Medical Technology, Suzhou Chien-shiung Institute of Technology Taicang 215411 Jiangsu Province P.R. China
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology Wuhan 430070 P.R. China.
RSC Adv. 2023 Mar 9;13(12):7952-7962. doi: 10.1039/d3ra00527e. eCollection 2023 Mar 8.
Cascade catalytic therapy has been recognized as a promising cancer treatment strategy, which is due in part to the induced tumor apoptosis when converting intratumoral hydrogen peroxide (HO) into highly toxic hydroxyl radicals (˙OH) based on the Fenton or Fenton-like reactions. Moreover this is driven by the efficient catalysis of glucose oxidization associated with starving therapy. The natural glucose oxidase (GO ), recognized as a "star" enzyme catalyst involved in cancer treatment, can specially and efficiently catalyze the glucose oxidization into gluconic acid and HO. Herein, pH-responsive biodegradable cascade therapeutic nanocomposites (FeO/GO -PLGA) with dual enzymatic catalytic features were designed to respond to the tumor microenvironment (TME) and to catalyze the cascade reaction (glucose oxidation and Fenton-like reaction) for inducing oxidase stress. The GO -motivated oxidation reaction could effectively consume intratumoral glucose to produce HO for starvation therapy and the enriched HO was subsequently converted into highly toxic ˙OH by a FeO-mediated Fenton-like reaction for chemodynamic therapy (CDT). In addition, the acidity amplification owing to the generation of gluconic acid will in turn accelerate the degradation of the nanocomposite and initiate the FeO-HO reaction for enhancing CDT. The resultant cooperative cancer therapy was proven to provide highly efficient tumor inhibition on HeLa cells with minimal systemic toxicity. This cascade catalytic Fenton nanocomposite might provide a promising strategy for efficient cancer therapy.
级联催化疗法已被公认为一种有前景的癌症治疗策略，部分原因在于基于芬顿或类芬顿反应将肿瘤内过氧化氢（HO）转化为高毒性羟基自由基（˙OH）时可诱导肿瘤细胞凋亡。此外，这是由与饥饿疗法相关的葡萄糖氧化的高效催化驱动的。天然葡萄糖氧化酶（GO ）被认为是癌症治疗中一种“明星”酶催化剂，它能特异性且高效地催化葡萄糖氧化为葡萄糖酸和HO。在此，设计了具有双重酶催化特性的pH响应性可生物降解级联治疗纳米复合材料（FeO/GO -PLGA），以响应肿瘤微环境（TME）并催化级联反应（葡萄糖氧化和类芬顿反应）来诱导氧化应激。由GO 引发的氧化反应可有效消耗肿瘤内葡萄糖以产生HO用于饥饿疗法，随后富集的HO通过FeO介导的类芬顿反应转化为高毒性的˙OH用于化学动力学疗法（CDT）。此外，由于葡萄糖酸生成导致的酸度增加反过来会加速纳米复合材料的降解并引发FeO-HO反应以增强CDT。结果表明，这种协同癌症治疗方法能在全身毒性最小的情况下对HeLa细胞提供高效的肿瘤抑制作用。这种级联催化芬顿纳米复合材料可能为高效癌症治疗提供一种有前景的策略。
