Photoimmunotherapy, which synergizes phototherapy and immunotherapy, holds significant potential for cancer treatment but demands more precise and effective strategies. Herein, we present a smart DNA hydrogel with energy-storing capabilities that responds to multiple tumor markers, enabling laser-free, on-demand photoimmunotherapy for localized melanoma treatment. The hydrogel is constructed from two single-stranded DNA chains via rolling-circle amplification, incorporating aptamers (Apt PD-1), oligonucleotides (CpG ODNs), and recognition sites for the HhaI endonuclease, enabling a controlled release of the photodynamic module. This module, composed of the AS1411 aptamer, a photosensitizer, and energy-storing persistent luminescent nanoparticles, facilitates selective tumor cell uptake and glutathione-triggered phototherapy in the absence of external irradiation, generating tumor-associated antigens for immunotherapy. Upon specific binding to T cells, Apt PD-1 blocks PD-1 receptors, promoting the release of CpG ODNs to enhance immunotherapy. In a murine melanoma model, the photoimmunotherapy system achieved a tumor inhibition rate of 73.3%. This laser-free, on-demand strategy based on the energy-storing DNA hydrogel offers a precise approach to cancer therapy and highlights the potential of DNA materials in advancing precision medicine.

中文翻译：

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智能储能 DNA 水凝胶用于黑色素瘤按需无激光光免疫治疗

光免疫疗法是光疗和免疫疗法的协同作用，在癌症治疗方面具有巨大潜力，但需要更精确和有效的策略。在此，我们提出了一种具有能量储存能力的智能 DNA 水凝胶，可响应多种肿瘤标志物，从而能够为局部黑色素瘤治疗提供无激光、按需光免疫疗法。水凝胶由两条单链 DNA 链通过滚环扩增构建而成，掺入适配体 （Apt PD-1）、寡核苷酸 （CpG ODN） 和 HhaI 核酸内切酶的识别位点，从而能够控制光动力模块的释放。该模块由 AS1411 适配体（一种光敏剂）和储能持续发光纳米颗粒组成，在没有外部照射的情况下促进选择性肿瘤细胞摄取和谷胱甘肽触发的光疗，产生用于免疫治疗的肿瘤相关抗原。与 T 细胞特异性结合后，Apt PD-1 阻断 PD-1 受体，促进 CpG ODN 的释放以增强免疫治疗。在小鼠黑色素瘤模型中，光免疫治疗系统实现了 73.3% 的肿瘤抑制率。这种基于储能 DNA 水凝胶的无激光按需策略为癌症治疗提供了一种精确的方法，并突出了 DNA 材料在推进精准医疗方面的潜力。