Au Nanoclusters and Photosensitizer Dual Loaded Spatiotemporal Controllable Liposomal Nanocomposites Enhance Tumor Photodynamic Therapy Effect by Inhibiting Thioredoxin Reductase
Au Nanoclusters and Photosensitizer Dual Loaded Spatiotemporal Controllable Liposomal Nanocomposites Enhance Tumor Photodynamic Therapy Effect by Inhibiting Thioredoxin Reductase
复制标题
金纳米团簇和光敏剂双负载时空可控脂质体纳米复合材料通过抑制硫氧还蛋白还原酶增强肿瘤光动力治疗效果
DOI：
10.1002/adhm.201601453
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发表时间：
2017-04-05
影响因子：
10
通讯作者：
Gao, Xueyun
中科院分区：
文献类型：
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作者：
Gao, Fuping;Zheng, Weiping;Gao, Xueyun
光动力疗法(PDT)是一种选择性高、副作用小的微创肿瘤治疗方法。然而，在长期的肿瘤控制方面，它通常并不有效。其中一个主要原因是肿瘤细胞形成了一些保护机制，帮助它们应对环境中的氧化应激。肿瘤中的硫氧还蛋白系统是一种重要的抗氧化防御系统。Au纳米团簇能有效抑制肿瘤细胞质中的硫氧还蛋白还原酶(TrxR)。在本论文中，金纳米团簇和光敏剂Cl6(Ce6)共负载到时空可控的脂质体纳米复合材料中。在低pH环境下，插入到脂双层中的pH响应分子对溶酶体内脂膜的不稳定性有很大的影响。然后，有效载荷可以迅速释放到细胞质中。Au纳米团簇能有效抑制胞浆TrxR，提高光动力诱导的细胞内活性氧自由基浓度，提高光动力治疗的效果。以乳腺癌为肿瘤模型，研究了金纳米团簇和光敏剂共载脂质体纳米复合材料对光动力疗法的体内外效应，并对其作用机制进行了探讨。本研究开拓了金纳米团簇的新应用，为提高光动力疗法的效果提供了新的思路。
Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure of tumors with high selectivity and low side effect. However, it is usually not efficient in long-lasting tumor control. One of the main reasons is tumor cells develop some protective mechanisms that help them to deal with oxidative stress in the environment. The thioredoxin system in cancer is an important antioxidant defense system. Au nanoclusters could effectively inhibit thioredoxin reductase (TrxR) in tumor cell cytoplasm. Herein, Au nanoclusters and photosensitizer Chlorine 6 (Ce6) are co-loaded in spatiotemporal controllable liposomal nanocomposites. pH responsive molecule inserted in lipid bilayer greatly contributes to the instability of the lipid membrane in lysosomal at low pH environment. Then the payloads can rapidly release into cytoplasm. Au nanoclusters effectively inhibit TrxR in cytoplasm and enhance the photodynamic-induced intracellular reactive oxygen-free radical concentration, improving the effect of PDT. Breast cancer is chosen as a tumor model and the Au nanoclusters and photosensitizer co-loaded liposomal nanocomposites are studied to improve the effect of PDT both in vitro and in vivo, and its corresponding mechanism is investigated. This study develops a new application of gold nanoclusters and provides a new train of thoughts for enhancing the effect of PDT.