Topical administration of siRNA, a clinically approved promising therapeutic modality, represents a much more transformative approach for drug development, compared to intravenous injection. To implement an efficient and extensive siRNA therapy , we engineered a rolling microneedle electrode array (RoMEA), which utilizes parallel circular blades with microneedle arrays on edge as electrodes. RoMEA integrates close-spaced microneedle electrodes and rolling structure to allow low-damage and large-area siRNA transfection. Upon applying RoMEA, regular micropores were established, efficient siRNA delivery and gene silence were achieved. In addition, employments of siRNA targeting programmed death-ligand 1 (PD-L1) alone, or combined with anti-programmed death-1 (PD-1) antibody or immunoadjuvant of CpG2395, in two tumor xenograft murine models demonstrated that proposed strategies restored efficient T cell immune response, conferring significant tumor growth inhibition with excellent safety profiles. RoMEA constitutes an unprecedented and ingenious clinic solution to large-area local delivery of nucleic acid for cancer immunotherapy.

中文翻译：

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滚动微针电极阵列（RoMEA）赋能核酸输送和癌症免疫治疗

siRNA 的局部给药是一种临床批准的有前途的治疗方式，与静脉注射相比，它代表了一种更具变革性的药物开发方法。为了实施高效、广泛的 siRNA 治疗，我们设计了滚动微针电极阵列 (RoMEA)，它利用边缘带有微针阵列的平行圆形刀片作为电极。 RoMEA集成了近距离微针电极和滚动结构，可实现低损伤、大面积的siRNA转染。应用RoMEA后，建立了规则的微孔，实现了高效的siRNA递送和基因沉默。此外，在两个肿​​瘤异种移植小鼠模型中，单独使用靶向程序性死亡配体 1 (PD-L1) 的 siRNA，或与抗程序性死亡 1 (PD-1) 抗体或 CpG2395 免疫佐剂联合使用，表明所提出的策略恢复了高效的 T 细胞免疫反应，具有显着的肿瘤生长抑制作用，并且具有出色的安全性。 RoMEA 为癌症免疫治疗的大面积局部核酸递送提供了前所未有的、巧妙的临床解决方案。