Transdermal cold atmospheric plasma-mediated immune checkpoint blockade therapy
Transdermal cold atmospheric plasma-mediated immune checkpoint blockade therapy
复制标题
经皮冷常压等离子体介导的免疫检查点阻断疗法
DOI：
10.1073/pnas.1917891117
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发表时间：
2020-02-18
影响因子：
11.1
通讯作者：
Gu, Zhen
中科院分区：
文献类型：
--
作者：
Chen, Guojun;Chen, Zhitong;Gu, Zhen
尽管免疫检查点阻断（ICB）疗法有望对抗癌症，但与低客观缓解率和严重的全身副作用相关的挑战仍然存在，并限制了其临床应用。在这里，我们描述了一种冷大气等离子体（CAP）介导的 ICB 疗法与微针（MN）相结合，用于 ICB 的透皮递送。我们发现中空结构的 MN (hMN) 贴片有助于 CAP 通过皮肤运输，导致肿瘤细胞死亡。肿瘤相关抗原的释放随后促进肿瘤引流淋巴结中树突状细胞的成熟，随后启动 T 细胞介导的免疫反应。 MN 贴片释放的抗程序性死亡配体 1 抗体 (aPDL1) 是一种免疫检查点抑制剂，可进一步增强抗肿瘤免疫力。我们的研究结果表明，所提出的经皮联合 CAP 和 ICB 疗法可以抑制原发肿瘤和远处肿瘤的肿瘤生长，延长荷瘤小鼠的生存期。
Despite the promise of immune checkpoint blockade (ICB) therapy against cancer, challenges associated with low objective response rates and severe systemic side effects still remain and limit its clinical applications. Here, we described a cold atmospheric plasma (CAP)-mediated ICB therapy integrated with microneedles (MN) for the transdermal delivery of ICB. We found that a hollow-structured MN (hMN) patch facilitates the transportation of CAP through the skin, causing tumor cell death. The release of tumor-associated antigens then promotes the maturation of dendritic cells in the tumor-draining lymph nodes, subsequently initiating T cell-mediated immune response. Anti-programmed death-ligand 1 antibody (aPDL1), an immune checkpoint inhibitor, released from the MN patch further augments the antitumor immunity. Our findings indicate that the proposed transdermal combined CAP and ICB therapy can inhibit the tumor growth of both primary tumors and distant tumors, prolonging the survival of tumor-bearing mice.