Photoactivated Self-Disassembly of Multifunctional DNA Nanoflower Enables Amplified Autophagy Suppression for Low-Dose Photodynamic Therapy
Photoactivated Self-Disassembly of Multifunctional DNA Nanoflower Enables Amplified Autophagy Suppression for Low-Dose Photodynamic Therapy
复制标题
多功能 DNA 纳米花的光激活自分解可增强低剂量光动力疗法的自噬抑制
DOI：
10.1002/smll.202104722
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发表时间：
2021-10-20
期刊：
影响因子：
13.3
通讯作者：
Zhang, Kaixiang
中科院分区：
文献类型：
--
作者：
Shi, Jinjin;Wang, Danyu;Zhang, Kaixiang
低剂量光动力疗法（PDT）在癌症治疗中对于减少不期望的患者光敏性具有很大的希望。然而，其治疗效果受到细胞内细胞保护过程如自噬的显著影响。本研究开发了一种高效的自噬抑制剂，它是一种多功能DNA纳米花（DNA nanoflower，DNF），由肿瘤靶向适体和DNA酶组成，用于沉默自噬相关基因，并经低剂量光敏剂（Ce 6）表面修饰。研究发现，多功能DNF能特异性靶向肿瘤细胞，在光照下产生活性氧（ROS），触发DNF的自分解，提高编码DNA酶的生物利用度，从而增强自噬抑制作用。作为一个简单的时空可编程的光基因治疗平台，设计的DNF能够抑制肿瘤生长，在体内用非常低的注射剂量的Ce 6（18 μ g kg（-1），约100倍低于一般应用的剂量），代表了一个有前途的策略，癌症治疗安全的低剂量PDT。
Low-dose photodynamic therapy (PDT) holds great promise for reducing undesired patient photosensitivity in cancer treatment. Yet, its therapeutic effect is significantly affected by intracellular cytoprotective processes, such as autophagy. Here, an efficient autophagy suppressor is developed, which is a multifunctional DNA nanoflower (DNF) consisted of tumor-targeting aptamers and DNAzymes for silencing autophagy-related genes, with surface modification of low-dose photosensitizer (Ce6). It is found that the multifunctional DNF can specifically target tumor cells and generate reactive oxygen species (ROS) under light irradiation to trigger self-disassembly of DNF, enhancing the bioavailability of encoded DNAzymes, leading to amplified autophagy suppression. As a facile spatiotemporally programmable photogene therapy platform, the designed DNF is able to suppress tumor growth in vivo with a very low injection dose of Ce6 (18 mu g kg(-1), around 100 times lower than the generally applied dose), representing a promising strategy for cancer therapy with safely low-dose PDT.