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近红外光触发的用于癌症成像和光免疫治疗的破坏细胞膜的纳米颗粒。

Nanoparticles destabilizing the cell membranes triggered by NIR light for cancer imaging and photo-immunotherapy.

作者信息

Tang Dongsheng, Cui Minhui, Wang Bin, Liang Ganghao, Zhang Hanchen, Xiao Haihua

机构信息

Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, PR China.

University of Chinese Academy of Sciences, Beijing, 100049, PR China.

出版信息

Nat Commun. 2024 Jul 17;15(1):6026. doi: 10.1038/s41467-024-50020-w.

Abstract

Cationic polymers have great potential for cancer therapy due to their unique interactions with cancer cells. However, their clinical application remains limited by their high toxicity. Here we show a cell membrane-targeting cationic polymer with antineoplastic activity (P) and a second near-infrared (NIR-II) fluorescent biodegradable polymer with photosensitizer Bodipy units and reactive oxygen species (ROS) responsive thioketal bonds (P). Subsequently, these two polymers can self-assemble into antineoplastic nanoparticles (denoted mt-NP) which could further accumulate at the tumor and destroy cell membranes through electrostatic interactions, resulting in cell membrane destabilization. Meanwhile, the photosensitizer Bodipy produces ROS to induce damage to cell membranes, proteins, and DNAs to kill cancer cells concertedly, finally resulting in cell membrane lysis and cancer cell death. This work highlights the use of near-infrared light to spatially and temporarily control cationic polymers for photodynamic therapy, photo-immunotherapy, and NIR-II fluorescence for bio-imaging.

摘要

阳离子聚合物因其与癌细胞的独特相互作用而在癌症治疗方面具有巨大潜力。然而,它们的临床应用仍受限于其高毒性。在此,我们展示了一种具有抗肿瘤活性的细胞膜靶向阳离子聚合物(P)以及一种带有光敏剂Bodipy单元和活性氧(ROS)响应硫酮键的近红外二区(NIR-II)荧光可生物降解聚合物(P)。随后,这两种聚合物可自组装成抗肿瘤纳米颗粒(称为mt-NP),其可通过静电相互作用进一步在肿瘤部位积聚并破坏细胞膜,导致细胞膜不稳定。同时,光敏剂Bodipy产生活性氧以诱导对细胞膜、蛋白质和DNA的损伤,协同杀死癌细胞,最终导致细胞膜裂解和癌细胞死亡。这项工作突出了利用近红外光在空间和时间上控制阳离子聚合物用于光动力治疗、光免疫治疗以及利用NIR-II荧光进行生物成像。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e1d/11255282/6389b564315b/41467_2024_50020_Fig1_HTML.jpg

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