Acid-Triggered Charge-Convertible Graphene-Based All-in-One Nanocomplex for Enhanced Genetic Phototherapy of Triple-Negative Breast Cancer
Acid-Triggered Charge-Convertible Graphene-Based All-in-One Nanocomplex for Enhanced Genetic Phototherapy of Triple-Negative Breast Cancer
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酸触发电荷转换石墨烯基一体化纳米复合物用于增强三阴性乳腺癌基因光疗
DOI：
10.1002/adhm.201901187
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发表时间：
2020
影响因子：
10
通讯作者：
Liu Yiyao
中科院分区：
文献类型：
--
作者：
Wu Chunhui;Tian Yuan;Zhang Yingxue;Xu Jiming;Wang Yikun;Guan Xiaotian;Li Tingting;Yang Hong;Li Shun;Qin Xiang;Liu Yiyao
用于癌症治疗的高效和刺激响应的纳米药物目前受到极大的关注。在这项研究中，通过用多层聚合物进行表面修饰并同时共转运光敏剂吲哚菁绿色（ICG）和miR-21的寡核苷酸抑制剂（miR-21 i），适当地设计了酸触发的电荷可逆的石墨烯基一体化纳米复合物，以实现以受控方式进行的高效遗传光疗。该纳米复合物（表示为GPCP/miR-21 i/ICG）有效地保护miR-21 i免于降解，并表现出优异的光热/光化学活性氧（ROS）产生以及荧光成像能力。与正常生理介质相比，货物ICG和miR-21 i可以在酸性pH下显著释放，并且由于酸触发的电荷反转效应而从内体/溶酶体逃逸。通常，释放的miR-21 i下调内源性miR-21并导致靶蛋白PTEN和Bax的上调，从而增加ICG的光疗效率。由于miR-21 i的遗传调控和ICG的光杀伤作用的组合，获得了针对MDA-MB-231三阴性乳腺癌（TNBC）模型的高体内抗癌效率。这项工作突出了这种智能纳米复合物作为基因-光联合治疗癌症的有吸引力的方式的巨大潜力，特别是对于难治性TNBC。
Highly efficient and stimulus‐responsive nanomedicines for cancer treatment are currently receiving tremendous attention. In this study, an acid‐triggered charge‐reversible graphene‐based all‐in‐one nanocomplex is appropriately designed by surface modification with multilayer polymers and simultaneous co‐transportation of photosensitizer indocyanine green (ICG) and oligonucleotide inhibitor of miR‐21 (miR‐21i) to achieve highly efficient genetic phototherapy in a controlled manner. The nanocomplex (denoted asGPCP/miR‐21i/ICG) effectively protects miR‐21i from degradation and exhibits excellent photothermal/photochemical reactive oxygen species (ROS) generation as well as fluorescence imaging ability. The cargoes ICG and miR‐21i can significantly be released at acidic pH compared with normal physiological medium and escaped from endosomes/lysosomes due to the acid‐triggered charge reversal effect. Typically, the released miR‐21i downregulate the endogenous miR‐21 and result in the upregulation of the target proteins PTEN and Bax, thus increasing the phototherapeutic efficiency of ICG. High in vivo anticancer efficiency against the MDA‐MB‐231 triple‐negative breast cancer (TNBC) model is obtained due to the combination of genetic regulation of miR‐21i and the photokilling effect of ICG. This work highlights the great potential of this smart nanocomplex as an attractive modality of gene‐photo combined treatment of cancer, especially for intractable TNBC.