JQ1-Loaded Polydopamine Nanoplatform Inhibits c-MYC/Programmed Cell Death Ligand 1 to Enhance Photothermal Therapy for Triple-Negative Breast Cancer
JQ1-Loaded Polydopamine Nanoplatform Inhibits c-MYC/Programmed Cell Death Ligand 1 to Enhance Photothermal Therapy for Triple-Negative Breast Cancer
复制标题
负载 JQ1 的聚多巴胺纳米平台抑制 c-MYC/程序性细胞死亡配体 1 以增强三阴性乳腺癌的光热疗法
DOI：
10.1021/acsami.9b18730
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发表时间：
2019-12-18
影响因子：
9.5
通讯作者：
Lu, Guangming
中科院分区：
文献类型：
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作者：
Tian, Ying;Wang, Xiaofen;Lu, Guangming
程序性细胞死亡配体1（PD-L1）阻断在癌症免疫治疗中取得了巨大成功;然而，三阴性乳腺癌（TNBC）对PD-L1抗体的反应有限。为了应对这一挑战，我们使用布罗莫结构域和末端外抑制剂JQ 1来下调PD-L1的表达，从而引发对TNBC的免疫应答，而不是使用抗体来阻断PD-L1。JQ 1还通过抑制BRD 4-c-MYC轴来抑制TNBC作为靶向治疗剂的生长。聚多巴胺纳米颗粒（PDMN）作为一种可生物降解和适应性平台引入，以负载JQ 1并诱导光热治疗（PTT）作为另一种协同治疗方式。由于JQ 1负载的PDMNs（PDMN-JQ 1）是自降解的，并且持续释放JQ 1，这种协同治疗可以导致细胞毒性T淋巴细胞的显著活化，并诱导强烈的免疫记忆效应，以保护小鼠免受肿瘤再攻击。总之，我们的研究证明了一种紧凑而简单的纳米平台，用于三联疗法，包括靶向疗法，PTT和免疫疗法，用于TNBC治疗。
Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy; however, the response of triple-negative breast cancer (TNBC) to PD-L1 antibodies is limited. To address this challenge, we use the bromodomain and extra-terminal inhibitor JQ1 to down-regulate the expression of PD-L1 and thus elicit the immune response to TNBC instead of using antibodies to block PD-L1. JQ1 also inhibits the growth of TNBC as a targeted therapeutic agent by inhibiting the BRD4-c-MYC axis. The polydopamine nanoparticles (PDMNs) are introduced as a biodegradable and adaptable platform to load JQ1 and induce photothermal therapy (PTT) as another synergistic therapeutic modality. Because the JQ1-loaded PDMNs (PDMN-JQ1) are self-degradable and release JQ1 continuously, this synergistic treatment can lead to remarkable activation of cytotoxic T lymphocytes and induce a strong immune-memory effect to protect mice from tumor re-challenge. Taken together, our study demonstrates a compact and simple nanoplatform for triple therapy, including targeted therapy, PTT, and immunotherapy, for TNBC treatment.