纳米医学
免疫疗法
光动力疗法
光敏剂
免疫系统
DNA
DNA损伤
药物输送
癌症免疫疗法
全身给药
dna疫苗
癌症研究
生物
材料科学
纳米技术
免疫学
化学
纳米颗粒
生物化学
体内
免疫
有机化学
生物技术
作者
Danyu Wang,Jingwen Liu,Jie Duan,Yongkang Ma,Hua Gao,Zhenzhong Zhang,Junjie Liu,Jinjin Shi,Kaixiang Zhang
标识
DOI:10.1021/acsami.2c12774
摘要
Immunotherapy is emerging as a paradigm-shifting modality for treatment cancer. However, systemic administration of immunomodulators is usually accompanied by extra-tumor toxicity and adverse immune effects. Precise delivery of immunomodulators with a highly controllable system may provide a solution for this issue. Here, we developed a photocontrolled DNA nanomedicine for localized delivery of DNA immunomodulators to enhance membrane-targeted photodynamic immunotherapy. Specifically, the DNA nanomedicine is composed of long tandemly repeated functional DNA sequences (PDL1 aptamers and CpG) with a photosensitizer (TMPyP4) inserted into the DNA structure, providing high drug-loading capacity. By blocking the surface PDL1 aptamer with a pHLIP-modified cDNA, the DNA nanomedicine does not induce any obvious immune response and can be specifically delivered and anchored to the tumor membrane. Under localized irradiation, photodynamically generated reactive oxygen species (ROS) causes breakage of DNA sequences, which triggers the collapse of the nanostructure and release of internal DNA immunomodulators. Under localized illumination, photodynamically generated ROS can cause DNA sequence breaks, triggering the collapse of nanostructures and the release of internal DNA immunomodulators thus enhancing membrane-targeted photodynamic immunotherapy. We have demonstrated that the developed DNA nanomedicine can drive efficient immune responses in tumor tissue without perceptibly interfering off-tumor immunity, resulting in efficient antitumor treatment while mitigating systemic toxicity.
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