物理化学学报 >> 2025, Vol. 41 >> Issue (10): 100113.doi: 10.1016/j.actphy.2025.100113

所属专题: 碳点功能材料

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细胞膜锚定的纳米工程化碳点作为焦亡放大器用于增强的肿瘤光动力免疫治疗

陈铁金1,3, 薛小矿1,3, 李建1,3, 崔敏辉2, 郝永梁1,3, 薛面起1, 肖海华2,*(), 葛介超1,3,*(), 汪鹏飞1,3   

  1. 1 中国科学院理化技术研究所, 北京 100190
    2 中国科学院化学研究所, 北京 100190
    3 中国科学院大学未来技术学院, 北京 100049
  • 收稿日期:2025-04-29 修回日期:2025-06-05 录用日期:2025-06-08 发布日期:2025-09-29
  • 通讯作者: Email: hhxiao@iccas.ac.cn (肖海华)jchge2010@mail.ipc.ac.cn (葛介超)
  • 基金资助:
    国家自然科学基金(52272052); 国家重点研发计划(2022YFA1207600)

Membrane-anchoring nanoengineered carbon dots as a pyroptosis amplifier for robust tumor photodynamic-immunotherapy

Tiejin Chen1,3, Xiaokuang Xue1,3, Jian Li1,3, Minhui Cui2, Yongliang Hao1,3, Mianqi Xue1, Haihua Xiao2,*(), Jiechao Ge1,3,*(), Pengfei Wang1,3   

  1. 1 Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
    2 Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
    3 School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2025-04-29 Revised:2025-06-05 Accepted:2025-06-08 Published:2025-09-29
  • Contact: Email: hhxiao@iccas.ac.cn (Haihua Xiao)jchge2010@mail.ipc.ac.cn (Jiechao Ge)
  • Supported by:
    the National Natural Science Foundation of China(52272052); the National Key Research and Development Program of China(2022YFA1207600)

摘要:

光动力疗法(PDT)作为一种美国食品药品监督管理局(FDA)批准的治疗手段,在肿瘤治疗领域取得了显著进展。然而,传统的PDT由于活性氧(ROS)的瞬时性、过度的光毒性以及诱导经典凋亡的特性,可能导致预后效果较差。本研究利用带正电荷的碳点光敏剂(PCDs)与新吲哚菁绿(IR820)之间的静电相互作用构建了一种纳米工程化碳点(NCDs)。通过调控IR820的引入比例,可改变NCDs的表面电荷与两亲性特征,从而优化其细胞膜锚定能力。此外,IR820的J聚集导致其荧光从NIR-Ⅰ区红移到NIR-Ⅱ区,从而实现NIR-Ⅱ成像。值得注意的是,IR820对PCDs的光活性具有淬灭作用,因此,NCDs的PDT效应依赖于750 nm激光照射下IR820的光漂白和577 nm激光照射下PCDs的光动力。最终,体外与体内实验均表明,在级联激光照射下,膜靶向的NCDs可以有效增强肿瘤细胞焦亡,从而以最小副作用实现肿瘤清除,同时激活免疫响应以抑制肿瘤的肺转移。本研究开发了一种多功能的纳米工程化碳点,提供了一种可控性强、治疗效果好以及安全性高的肿瘤光动力免疫治疗新策略,展现出良好的临床应用前景。

关键词: 碳点, 细胞膜靶向, 近红外二区发射, 光控焦亡, 光动力免疫治疗

Abstract:

Photodynamic therapy (PDT), as a Food and Drug Administration (FDA)-approved therapeutic modality, has witnessed substantial advancements in the field of oncology. However, the conventional PDT may suffer poor prognosis due to the transient nature of (Reactive Oxygen Species) ROS, excessive phototoxicity, and inducing traditional apoptosis. In this study, a nanoengineered carbon dots (NCDs) was constructed through electrostatic interaction between a positive-charged carbon dots photosensitizers (PCDs) and new indocyanine green (IR820). The introduction of IR820 at variable ratios could change the surface charge and amphiphilic characteristics of NCDs, thereby modulating the membrane-anchoring capability of NCDs. Besides, the J-aggregation of IR820 led to a redshift of fluorescence from NIR-Ⅰ to NIR-Ⅱ region, thereby achieving NIR-Ⅱ imaging. Furthermore, the photoactivity of PCDs was quenched by IR820, with subsequent restoration of PDT occurring contingent on the photobleaching of IR820 via 750 nm laser irradiation. Finally, both in vitro and in vivo studies had demonstrated that under a cascaded laser irradiation, the membrane-targeted NCDs could effectively induce cell pyroptosis, thereby eradicating tumors with minimal side effects while simultaneously activating immune responses to inhibit tumor lung metastasis. This study developed a multifunctional nanoengieering carbon dots and offered novel perspectives for tumor photodynamic-immunotherapy with enhanced controllability, improved efficacy and high security.

Key words: Carbon dots, Cell membrane targeting, Near-infrared-Ⅱ emission, Photon-controlled pyroptosis, Photodynamic-immunotherapy