Harnessing the power of traceable system C-GAP: homologous-targeting to fire up T-cell immune responses with low-dose irradiation.

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Weijie Zhuang, Kuangwu Pan, Jie Wu, Leyi Liu, Shiyu Lv, Jiajun Hu, Fangyang Shi, Wei Zhao, Dongsheng Yu
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引用次数: 0

Abstract

While radiotherapy-induced immunogenic cell death (ICD) holds potential for enhancing cancer immunotherapy, the conventional high-dose irradiation often leads to an immunosuppressive microenvironment and systemic toxicity. Therefore, a biomimetic nanoplatform cell membrane coated-nitrogen-doped graphene quantum dots combined with Au nanoparticles (C-GAP) was developed in this study. Firstly, homologous and traceable targeting features of C-GAP enables tumor-selective accumulation, providing reference for the selection of the timing of radiotherapy. Secondly, radiosensitization by C-GAP with Low-dose irradiation (LDI) amplifies reactive oxygen species (ROS) generation to trigger potent ICD. Thirdly, remarkable immune remodeling induced by C-GAP enhances CD8+ T cell infiltration and effector function. Single-cell RNA sequencing revealed that C-GAP-LDI combination upregulates TNF and CCL signaling pathway expression in tumor-infiltrating CD8+ T cells which potentiates tumor eradication. Our findings present a novel approach for safe and effective radioimmunotherapy, where C-GAP sensitized LDI achieves therapeutic enhancement through precise ICD induction and systemic immune activation.

利用可追踪系统C-GAP的力量:同源靶向在低剂量照射下激发t细胞免疫反应。
虽然放射治疗诱导的免疫原性细胞死亡(ICD)具有增强癌症免疫治疗的潜力,但传统的高剂量照射通常会导致免疫抑制微环境和全身毒性。因此,本研究开发了一种仿生纳米平台细胞膜-氮掺杂石墨烯量子点结合金纳米颗粒(C-GAP)。首先,C-GAP具有同源性和可追溯性的靶向特性,可实现肿瘤选择性蓄积,为放疗时机的选择提供参考。其次,低剂量辐照(LDI)下C-GAP的放射增敏会增加活性氧(ROS)的产生,从而引发强效ICD。第三,C-GAP诱导的显著免疫重塑增强了CD8+ T细胞的浸润和效应细胞的功能。单细胞RNA测序显示,C-GAP-LDI联合上调肿瘤浸润性CD8+ T细胞中TNF和CCL信号通路的表达,从而增强肿瘤的根除。我们的研究结果提出了一种安全有效的放射免疫治疗新方法,其中C-GAP致敏LDI通过精确的ICD诱导和全身免疫激活来实现治疗增强。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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