Key Laboratory of Smart Biomaterials of Zhejiang Province, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Photonics Research Institute, Department of Electrical and Electronic Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
Sci Bull (Beijing). 2023 Nov 30;68(22):2779-2792. doi: 10.1016/j.scib.2023.10.004. Epub 2023 Oct 16.
Immunotherapy has revolutionized cancer therapy, using chemical or biological agents to reinvigorate the immune system. However, most of these agents have poor tumor penetration and inevitable side effects that complicate therapeutic outcomes. Electrical stimulation (ES) is a promising alternative therapy against cancers that does not involve chemical or biological agents but is limited in the fabrication and operation of complex micrometer-scale ES devices. Here, we present an optically microprinted flexible interdigital electrode with a gold-plated polymer microneedle array to generate alternating electric fields for cancer treatment. A flexible microneedle-array-integrated interdigital electrode (FMIE) was fabricated by combining optical 3D microprinting and electroless plating processes. FMIE-mediated ES of cancer cells induced necrotic cell death through mitochondrial Ca overload and increased intracellular reactive oxygen species (ROS) production. This led to the release of damage-associated molecular patterns that activated the immune response and potentiated immunogenic cell death (ICD). FMIE-based ES has an excellent safety profile and systemic anti-tumor effects, inhibiting the growth of primary and distant tumors as well as melanoma lung metastasis. FMIE-based ES-driven cancer immunomodulation provides a new pathway for drug-free cancer therapy.
免疫疗法已经彻底改变了癌症治疗，利用化学或生物制剂来重振免疫系统。然而，这些制剂大多数穿透肿瘤的能力差，并且不可避免地存在副作用，这使得治疗效果复杂化。电刺激（ES）是一种很有前途的抗癌替代疗法，它不涉及化学或生物制剂，但在制造和操作复杂的微尺度 ES 设备方面存在局限性。在这里，我们提出了一种基于光微打印的柔性叉指电极，该电极带有镀金聚合物微针阵列，可产生用于癌症治疗的交变电场。通过结合光学 3D 微打印和化学镀工艺，制造了一种集成微针阵列的叉指电极（FMIE）。FMIE 介导的癌细胞 ES 通过线粒体 Ca 超载和增加细胞内活性氧（ROS）的产生导致坏死性细胞死亡。这导致了损伤相关分子模式的释放，激活了免疫反应并增强了免疫原性细胞死亡（ICD）。基于 FMIE 的 ES 具有极好的安全性和系统抗肿瘤作用，抑制原发性和远处肿瘤以及黑色素瘤肺转移的生长。基于 FMIE 的 ES 驱动的癌症免疫调节为无药物癌症治疗提供了新途径。
