Wang Yuanwei, Chen Penghang, Wen Haifei, Gui Yixiong, Yan Dingyuan, Huang Di, Wang Dong, Tang Ben Zhong, Tan Hui
Center for Child Care and Mental Health (CCCMH), Shenzhen Children's Hospital, Shenzhen 518034, China.
Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, China.
ACS Nano. 2024 Dec 3;18(48):33168-33180. doi: 10.1021/acsnano.4c11757. Epub 2024 Nov 19.
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.
免疫疗法与光疗法相结合正成为一种治疗全能癌症的有前景的策略。在本研究中，将成簇规律间隔短回文重复序列（CRISPR）相关蛋白9（Cas9）系统、聚集诱导发光（AIE）光敏剂（PS）以及聚乙烯亚胺/透明质酸表面涂层相结合，构建了一种多功能纳米平台，称为TCPH纳米颗粒（NPs），用于癌症的综合诊疗。TCPH NPs具有多种内在功能，包括高效产生活性氧（ROS）、良好的光热转换、程序性死亡配体1（PD-L1）消除能力以及有效的细胞内转运。产生的ROS和热疗不仅能消除原发性肿瘤，还能调节肿瘤免疫微环境。PD-L1的基因组破坏显著增强了其治疗效果，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。在多种肿瘤模型中证实了优异的诊疗性能，这意味着这种光诊疗与免疫疗法的协同策略为新兴的CRISPR介导的纳米药物带来了范式转变。
