Immunotherapy combined with phototherapy is emerging as a promising strategy to treat omnipotent cancers. In this study, a clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) system, aggregation-induced emission (AIE) photosensitizer (PS) and surface coating of polyethylene imine/hyaluronic acid were combined to construct a multifunctional nanoplatform, denoted as TCPH nanoparticles (NPs), for comprehensive cancer theranostics. TCPH NPs are featured by intrinsic functions including efficient reactive oxygen species (ROS) production, good photothermal conversion, programmed death-ligand 1 (PD-L1)-eliminating capability, and effective intracellular transport. The generated ROS and hyperthermia do not only achieve primary tumor elimination but also regulate the tumor immune microenvironment. Genomic disruption of PD-L1 conspicuously augments its therapeutic efficacy, especially in tumor metastasis and recurrence. Exceptional multimodal imaging navigation has also been developed. Excellent theranostics performance was substantiated in diverse tumor models, implying that this synergistic strategy of phototheranostics and immunotherapy provides a paradigm shift in emerging CRISPR-mediated nanomedicines.

中文翻译：

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由 CRISPR-Cas9 和聚集诱导发射光敏剂介导的先进纳米平台促进癌症治疗诊断学


免疫疗法联合光疗正在成为治疗全能癌症的一种有前途的策略。在本研究中，将成簇的规则间隔短回文重复序列 （CRISPR） 相关蛋白 9 （Cas9） 系统、聚集诱导发射 （AIE） 光敏剂 （PS） 和聚乙烯亚胺/透明质酸的表面涂层相结合，构建了一个多功能纳米平台，表示为 TCPH 纳米颗粒 （NPs），用于综合癌症治疗诊断学。TCPH NPs 具有内在功能，包括高效的活性氧 （ROS） 产生、良好的光热转化、程序性死亡配体 1 （PD-L1） 消除能力和有效的细胞内运输。产生的 ROS 和热疗不仅可以实现原发性肿瘤消除，还可以调节肿瘤免疫微环境。PD-L1 的基因组破坏显着增强了其治疗效果，尤其是在肿瘤转移和复发方面。还开发了出色的多模态成像导航。出色的治疗诊断学性能在不同的肿瘤模型中得到证实，这意味着光疗诊断学和免疫疗法的这种协同策略为新兴的 CRISPR 介导的纳米药物提供了范式转变。