肿瘤微环境
肿瘤缺氧
缺氧(环境)
纳米载体
光动力疗法
免疫疗法
癌症研究
遗传增强
免疫系统
生物
材料科学
化学
基因
药物输送
纳米技术
免疫学
医学
放射治疗
氧气
生物化学
肿瘤细胞
内科学
有机化学
作者
Suchen Qu,Yukui Zhang,Lu Fan,Tao Yan,Gaoshuang Zhu,Hongxiu Song,Kaiyong Yang,Xin Han
标识
DOI:10.1002/adhm.202302615
摘要
Abstract Hypoxia is a key hallmark of solid tumors and can cause resistance to various treatments such as photodynamics and immunotherapy. Microenvironment‐responsive gene editing provides a powerful tool to overcome hypoxia resistance and remodel hypoxic microenvironments for enhanced tumor therapy. Here, a light‐enhanced hypoxia‐responsive multifunctional nanocarrier is developed to perform spatiotemporal specific dual gene editing for enhanced photodynamic and immunotherapy in breast cancer. As a gated molecule of nanocarrier, the degradation of azobenzene moieties under hypoxic conditions triggers controllable release of Cas9 ribonucleoprotein in hypoxic site of the tumor. Hyaluronic acid is conjugated with chloramine e6 to coat mesoporous silica nanoparticles for targeted delivery in tumors and generation of high levels of reactive oxygen species, which can result in increased hypoxia levels for effective cleavage of azobenzene bonds to improve gene editing efficiency and reduce toxic side effects with light irradiation. Moreover, dual targeting HIF‐1α and PD‐L1 in the anoxic microenvironments can overcome hypoxia resistance and remodel immune microenvironments, which reduces tumor plasticity and resistance to photodynamic and immunotherapy. In summary, a light‐enhanced hypoxia responsive nanocomposite is developed for controllable gene editing which holds great promise for synergistic hypoxia‐resistant photodynamic and immunotherapy.
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