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

• Published in: Nature communications Vol. 15; no. 1; pp. 6026 - 21
• Main Authors: Tang, Dongsheng, Cui, Minhui, Wang, Bin, Liang, Ganghao, Zhang, Hanchen, Xiao, Haihua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.07.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1059/153; 631/67/1059/2325; 631/67/2321; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biodegradation; Boron Compounds - chemistry; Boron Compounds - pharmacology; Cancer; Cancer therapies; Cationic polymerization; Cell death; Cell Line, Tumor; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell membranes; Damage accumulation; Destabilization; Electrostatic properties; Female; Fluorescence; Humanities and Social Sciences; Humans; I.R. radiation; Imaging; Immunotherapy; Immunotherapy - methods; Infrared Rays; Irradiation; Lysis; Membranes; Mice; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Near infrared radiation; Neoplasms - diagnostic imaging; Neoplasms - drug therapy; Neoplasms - therapy; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Polymers; Polymers - chemistry; Reactive oxygen species; Reactive Oxygen Species - metabolism; Science; Science (multidisciplinary); Toxicity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-50020-w

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 mt ) and a second near-infrared (NIR-II) fluorescent biodegradable polymer with photosensitizer Bodipy units and reactive oxygen species (ROS) responsive thioketal bonds (P Bodipy ). Subsequently, these two polymers can self-assemble into antineoplastic nanoparticles (denoted mt-NP Bodipy ) 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. The application of synthetic polymeric nanoparticles for cancer therapy is limited by its biosafety and targeting ability. Here the authors report cationic nanoparticles that anchor and destabilize cancer cell membranes upon NIR-II irradiation for photo-immunotherapy and imaging.