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用 FeAu-亚甲蓝复合物的功能性活体材料增强冷肿瘤中的免疫原性细胞死亡

英文原题:Potentiating Immunogenic Cell Death in Cold Tumor with Functional Living Materials of FeAu-Methylene Blue Composites.

查看英文原题

Potentiating Immunogenic Cell Death in Cold Tumor with Functional Living Materials of FeAu-Methylene Blue Composites.

PubMed 2024/02/27(内容时间) Adv Healthc Mater Q1 · IF 11(JCR 2025)

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中文摘要

免疫冷肿瘤的低免疫原性、缺乏TIL(肿瘤浸润淋巴细胞)以及免疫抑制微环境是导致不良预后的主要瓶颈。在此,开发了一种整合的肿瘤生物成像与多模式治疗策略,通过调节氧化应激水平、增强光杀伤效力、诱导免疫原性细胞死亡以及抑制免疫检查点,将免疫冷肿瘤转化为热肿瘤。

在此过程中,可利用独特的肿瘤微环境,从金属离子Fe(II)和Au(III)原位生物合成自组装铁配合物和荧光金纳米簇,用于肿瘤的主动靶向和实时可视化,同时通过类过氧化物酶活性调节肿瘤内的活性氧水平。

此外,亚甲蓝(MB)介导的光动力疗法促进损伤相关分子模式(DAMPs)的释放,其作为原位肿瘤疫苗,进一步诱导树突状细胞成熟,增强抗肿瘤T细胞的浸润,并显著阻碍原发肿瘤的生长和增殖。更引人注目的是,通过与程序性细胞死亡受体-1(PD-1)检查点抑制剂协同作用,免疫抑制微环境被重塑,模型小鼠的生存时间得以延长。

总之,该范式利用肿瘤特异性微环境来激发强大而持久的全身抗肿瘤免疫,为精准癌症诊疗提供了新的机遇。

展开英文摘要原文

Low immunogenicity, absence of tumor-infiltrating lymphocytes and immunosuppressive microenvironment of immune cold tumors are the main bottlenecks leading to unfavorable prognosis.

Here, an integrated tumor bioimaging and multimodal therapeutic strategy is developed, which converts immune cold into hot by modulating oxidative stress levels, enhancing photo-killing efficacy, inducing immunogenic cell death and inhibiting the immune checkpoint.

On that occasion, the unique tumor microenvironment can be harnessed to biosynthesize in situ self-assembly iron complexes and fluorescent gold nanoclusters from metal ions Fe(II) and Au(III) for active targeting and real-time visualization of the tumors, simultaneously regulating reactive oxygen species levels within tumors via peroxidase-like activity.

Furthermore, methylene blue (MB)-mediated photodynamic therapy promotes the release of damage-associated molecular patterns (DAMPs), which acts as in situ tumor vaccine and further induces dendritic cells maturation, augments the infiltration of antitumor T cells and significantly impedes the primary tumor growth and proliferation.

More strikingly, by synergizing with the programmed cell death receptor-1 (PD-1) checkpoint inhibitor, the immunosuppressive microenvironment is remodeled and the survival time of model mice is prolonged. In summary, this paradigm utilizes the tumor-specific microenvironment to boost robust and durable systemic antitumor immunity, providing a novel opportunity for precision cancer theranostics.

论文信息

作者
Wang T、Wang Y、Liu T、Yu F、Liu L、Xiong H、Xu W、Fan X
第一作者单位
Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.China
通讯作者单位
State Key Laboratory of Digital Medical Engineering, National Demonstration Center for Experimental Biomedical Engineering Education School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.China
文献类型
非美国政府资助研究
期刊
Advanced healthcare materials2024 Jun
原文标识
PubMed 38381808 · DOI 10.1002/adhm.202302767