Duo of (-)-epigallocatechin-3-gallate and doxorubicin loaded by polydopamine coating ZIF-8 in the regulation of autophagy for chemo-photothermal synergistic therapy
Duo of (-)-epigallocatechin-3-gallate and doxorubicin loaded by polydopamine coating ZIF-8 in the regulation of autophagy for chemo-photothermal synergistic therapy
复制标题
聚多巴胺涂层 ZIF-8 负载 (-)-表没食子儿茶素-3-没食子酸酯和阿霉素二重奏在化疗光热协同治疗中调节自噬的作用
DOI：
10.1039/c9bm01614g
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发表时间：
2020-03-07
影响因子：
6.6
通讯作者：
Fang, Wenjun
中科院分区：
文献类型：
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作者：
Chen, Xuerui;Tong, Rongliang;Fang, Wenjun
为了实现高度的全身性治疗功效，化学疗法与光热疗法组合用于化学-光热协同疗法;然而，该策略遭受高毒性和对癌细胞的不令人满意的敏感性。在此，我们开发了一种pH和光热响应性沸石咪唑酯框架（ZIF-8）化合物，用于在肿瘤部位负载双药并提高其疗效。由于自噬总是伴随着肿瘤的进展和转移，因此对与自噬的调节相关的抗癌治疗存在未满足的需求。采用聚多巴胺（PDA）包被ZIF-8（EGCG@ZIF-PDA-PEG-DOX，简称EZPPD），通过分级自组装的方法将具有抗癌活性的绿色茶多酚（-）-表没食子儿茶素没食子酸酯（EGCG）和阿霉素（DOX）双重负载到ZIF-8上。PDA在近红外（NIR）激光照射下可以传递光热能量，提高温度。由于其pH响应，EZPPD在肿瘤微环境中释放EGCG和DOX，其中温度在PDA和NIR激光照射的帮助下升高。DOX和EGCG的双重作用可诱导自噬流并加速自噬体的形成。在小鼠HeLa肿瘤模型中，光热化学疗法可以具有显著的协同作用，并增强其抗癌功效。因此，结果表明，EZPPD呈现出临床上有希望的候选人的关键特征，以解决与协同化疗和光热利用在抗肿瘤治疗中的挑战。
To achieve highly systemic therapeutic efficacy, chemotherapy is combined with photothermal therapy for chemo-photothermal synergistic therapy; however, this strategy suffers from high toxicity and unsatisfactory sensitivity for cancer cells. Herein, we developed a pH- and photothermal-responsive zeolitic imidazolate framework (ZIF-8) compound for loading a dual-drug in the tumor site and improving their curative effects. Since autophagy always accompanies tumor progression and metastasis, there is an unmet need for an anticancer treatment related to the regulation of autophagy. Green tea polyphenols, namely, (-)-epigallocatechin-3-gallate (EGCG) and doxorubicin (DOX), both of which exhibit anticancer activity, were dual-loaded via polydopamine (PDA) coating ZIF-8 (EGCG@ZIF-PDA-PEG-DOX, EZPPD for short) through hierarchical self-assembly. PDA could transfer photothermal energy to increase the temperature under near-infrared (NIR) laser irradiation. Due to its pH-response, EZPPD released EGCG and DOX in the tumor microenvironment, wherein the temperature increased with the help of PDA and NIR laser irradiation. The duo of DOX and EGCG induced autophagic flux and accelerated the formation of autophagosomes. In a mouse HeLa tumor model, photothermal-chemotherapy could ablate the tumor with a significant synergistic effect and potentiate the anticancer efficacy. Thus, the results indicate that EZPPD renders the key traits of a clinically promising candidate to address the challenges associated with synergistic chemotherapy and photothermal utilization in antitumor therapy.