PDF(Pubmed)
Abstract：
As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu2+, 3,3\'-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer.
摘要：
作为一种新兴的癌症治疗策略，由于缺氧和肿瘤微环境中谷胱甘肽（GSH）的过度表达，基于活性氧的肿瘤催化疗法面临巨大挑战。在这里，一个自组装的铜基纳米平台，TCCHA,设计用于酶样催化增强的化学动力学/光动力学/抗血管生成三药治疗肝细胞癌。TCCHA由Cu2+制成，3,3'-二硫代双（丙酰肼），和光敏剂氯e6通过简单的一锅法自组装策略，之后涂覆醛透明质酸，然后加载抗血管药物AL3818。所得TCCHA纳米粒表现出pH/GSH双响应释药行为和多酶活性,包括芬顿,谷胱甘肽过氧化物酶-，和过氧化氢酶样活性。TCCHA,氧化还原稳态破坏剂，促进·OH生成和GSH消耗，从而提高化学动力学疗法的疗效。TCCHA,具有过氧化氢酶样活性，还可以通过放大O2的产生来增强光动力疗法的功效。在体内,TCCHA有效抑制肿瘤血管生成并抑制肿瘤生长，而没有明显的全身毒性。总的来说,这项研究提出了一种制备多酶样纳米颗粒的简单策略，和TCCHA纳米颗粒在酶催化增强的化学动力学/光动力学/抗血管生成三联疗法中显示出巨大的潜力。
