NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell death
Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by...
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KeAi Communications Co., Ltd.
2025-04-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24005553 |
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| author | Tian Zhang Dongsheng Tang Pengfei Wu Shaoping Jiang Yuquan Zhang Abid Naeem Yong Li Chunhui Li Bo Hu Shuai Guo Caixia Sun Haihua Xiao Ran Yan Yuhua Weng Yuanyu Huang |
| author_facet | Tian Zhang Dongsheng Tang Pengfei Wu Shaoping Jiang Yuquan Zhang Abid Naeem Yong Li Chunhui Li Bo Hu Shuai Guo Caixia Sun Haihua Xiao Ran Yan Yuhua Weng Yuanyu Huang |
| author_sort | Tian Zhang |
| collection | DOAJ |
| description | Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy. |
| format | Article |
| id | doaj-art-baadea56a80f473193e96dcfbc591fb5 |
| institution | DOAJ |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-baadea56a80f473193e96dcfbc591fb52025-08-20T03:11:54ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-04-014628530010.1016/j.bioactmat.2024.12.018NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell deathTian Zhang0Dongsheng Tang1Pengfei Wu2Shaoping Jiang3Yuquan Zhang4Abid Naeem5Yong Li6Chunhui Li7Bo Hu8Shuai Guo9Caixia Sun10Haihua Xiao11Ran Yan12Yuhua Weng13Yuanyu Huang14School of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, ChinaBeijing National Laboratory for Molecular Science Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Science Beijing 100190, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, ChinaSchool of Chemistry, Chemical Engineering & Biotechnology, Nanyang Technological University, 637371, SingaporeBeijing National Laboratory for Molecular Science Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Science Beijing 100190, ChinaKey Laboratory of Biomedical Functional Materials, School of Science, China Pharmaceutical University, Nanjing, 211198, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China; Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology (BIT), Zhuhai 519088, China; Advanced Technology Research Institute, Beijing Institute of Technology (BIT), Jinan 250101, ChinaSchool of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China; Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology (BIT), Zhuhai 519088, China; Advanced Technology Research Institute, Beijing Institute of Technology (BIT), Jinan 250101, China; Corresponding author. School of Life Science, Advanced Research Institute of Multidisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China.Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy.http://www.sciencedirect.com/science/article/pii/S2452199X24005553siRNAPolymer nanoparticlesPD-L1 silencingPhotodynamic therapyImmunotherapy |
| spellingShingle | Tian Zhang Dongsheng Tang Pengfei Wu Shaoping Jiang Yuquan Zhang Abid Naeem Yong Li Chunhui Li Bo Hu Shuai Guo Caixia Sun Haihua Xiao Ran Yan Yuhua Weng Yuanyu Huang NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell death Bioactive Materials siRNA Polymer nanoparticles PD-L1 silencing Photodynamic therapy Immunotherapy |
| title | NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell death |
| title_full | NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell death |
| title_fullStr | NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell death |
| title_full_unstemmed | NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell death |
| title_short | NIR-II photo-accelerated polymer nanoparticles boost tumor immunotherapy via PD-L1 silencing and immunogenic cell death |
| title_sort | nir ii photo accelerated polymer nanoparticles boost tumor immunotherapy via pd l1 silencing and immunogenic cell death |
| topic | siRNA Polymer nanoparticles PD-L1 silencing Photodynamic therapy Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24005553 |
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