Smart Energy-Storing DNA Hydrogel for On-Demand Laser-Free Photoimmunotherapy of Melanoma
Huaixin Zhao, Lijun Wang, Sen Yang, Zhuiyun Li, Xiaocui Guo, Zuo Chen, Guoming Xie, Chi Yao, Dayong Yang
Abstract
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 Hha I 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.