Curcumin-based polymer prodrug nanoplatform for high-efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemness
Abstract Background Immunotherapy represents a transformative advance in cancer treatment; however, its efficacy in head and neck cancer (HNC) remains constrained by tumor cell stemness and profound immunosuppression within the tumor microenvironment (TME). Overcoming these barriers necessitates inn...
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BMC
2025-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03559-9 |
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| author | Zhisen Shen Hao Jiang Shuaijun Lu Hailong Tian Feng Gao Hongxia Deng Canhua Huang |
| author_facet | Zhisen Shen Hao Jiang Shuaijun Lu Hailong Tian Feng Gao Hongxia Deng Canhua Huang |
| author_sort | Zhisen Shen |
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| description | Abstract Background Immunotherapy represents a transformative advance in cancer treatment; however, its efficacy in head and neck cancer (HNC) remains constrained by tumor cell stemness and profound immunosuppression within the tumor microenvironment (TME). Overcoming these barriers necessitates innovative strategies to simultaneously eradicate stem-like populations and reprogram the TME. Methods We engineered a tumor-targeted polymer prodrug nanoplatform, Biotin@P-Cur/T780 NPs, integrating disulfide-linked polycurcumin (P-Cur) and the photothermal agent T780. DSPE-PEG-Biotin surface functionalization enables active tumor targeting. The nanoplatform exploits high intratumoral glutathione (GSH) to trigger disassembly, releasing curcumin monomers and T780. This elicits dual GSH depletion and reactive oxygen species (ROS) amplification, inducing ROS-mediated apoptosis and ferroptosis. Concurrently, localized near-infrared irradiation activates T780, synergizing photothermal (PTT) and photodynamic (PDT) therapies to intensify immunogenic cell death (ICD). Results The Biotin@P-Cur/T780 NPs potently suppressed tumor cell stemness in vitro and in vivo. ROS/ferroptosis-driven ICD, amplified by PTT/PDT, reversed TME immunosuppression, enhancing dendritic cell maturation and cytotoxic T lymphocyte infiltration. This multimodal mechanism significantly inhibited primary tumor growth and metastasis in HNC models, while extending survival. Conclusion Our prodrug nanoplatform overcomes key resistance mechanisms in HNC by coordinately targeting stemness, inducing dual apoptosis/ferroptosis, and potentiating ICD through PDT/PTT-enhanced immunomodulation. This strategy provides a potent combinatorial approach to augment immunotherapy efficacy in refractory tumors. |
| format | Article |
| id | doaj-art-37e304c46d9e4ea1a5fee2720948c45c |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-37e304c46d9e4ea1a5fee2720948c45c2025-08-20T04:02:55ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123111410.1186/s12951-025-03559-9Curcumin-based polymer prodrug nanoplatform for high-efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemnessZhisen Shen0Hao Jiang1Shuaijun Lu2Hailong Tian3Feng Gao4Hongxia Deng5Canhua Huang6Department of Otolaryngology-Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo UniversityThe Second Affiliated Hospital of Harbin Medical UniversityThe First Affiliated Hospital of Ningbo UniversityState Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan UniversityThe Second Affiliated Hospital of Harbin Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo UniversityState Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan UniversityAbstract Background Immunotherapy represents a transformative advance in cancer treatment; however, its efficacy in head and neck cancer (HNC) remains constrained by tumor cell stemness and profound immunosuppression within the tumor microenvironment (TME). Overcoming these barriers necessitates innovative strategies to simultaneously eradicate stem-like populations and reprogram the TME. Methods We engineered a tumor-targeted polymer prodrug nanoplatform, Biotin@P-Cur/T780 NPs, integrating disulfide-linked polycurcumin (P-Cur) and the photothermal agent T780. DSPE-PEG-Biotin surface functionalization enables active tumor targeting. The nanoplatform exploits high intratumoral glutathione (GSH) to trigger disassembly, releasing curcumin monomers and T780. This elicits dual GSH depletion and reactive oxygen species (ROS) amplification, inducing ROS-mediated apoptosis and ferroptosis. Concurrently, localized near-infrared irradiation activates T780, synergizing photothermal (PTT) and photodynamic (PDT) therapies to intensify immunogenic cell death (ICD). Results The Biotin@P-Cur/T780 NPs potently suppressed tumor cell stemness in vitro and in vivo. ROS/ferroptosis-driven ICD, amplified by PTT/PDT, reversed TME immunosuppression, enhancing dendritic cell maturation and cytotoxic T lymphocyte infiltration. This multimodal mechanism significantly inhibited primary tumor growth and metastasis in HNC models, while extending survival. Conclusion Our prodrug nanoplatform overcomes key resistance mechanisms in HNC by coordinately targeting stemness, inducing dual apoptosis/ferroptosis, and potentiating ICD through PDT/PTT-enhanced immunomodulation. This strategy provides a potent combinatorial approach to augment immunotherapy efficacy in refractory tumors.https://doi.org/10.1186/s12951-025-03559-9Head and neck cancerCurcumin-based nanoplatformImmunotherapyTumor cell stemnessImmunogenic cell death (ICD) |
| spellingShingle | Zhisen Shen Hao Jiang Shuaijun Lu Hailong Tian Feng Gao Hongxia Deng Canhua Huang Curcumin-based polymer prodrug nanoplatform for high-efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemness Journal of Nanobiotechnology Head and neck cancer Curcumin-based nanoplatform Immunotherapy Tumor cell stemness Immunogenic cell death (ICD) |
| title | Curcumin-based polymer prodrug nanoplatform for high-efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemness |
| title_full | Curcumin-based polymer prodrug nanoplatform for high-efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemness |
| title_fullStr | Curcumin-based polymer prodrug nanoplatform for high-efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemness |
| title_full_unstemmed | Curcumin-based polymer prodrug nanoplatform for high-efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemness |
| title_short | Curcumin-based polymer prodrug nanoplatform for high-efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemness |
| title_sort | curcumin based polymer prodrug nanoplatform for high efficiency immunotherapy by synergistically suppression of head and neck cancer cell stemness |
| topic | Head and neck cancer Curcumin-based nanoplatform Immunotherapy Tumor cell stemness Immunogenic cell death (ICD) |
| url | https://doi.org/10.1186/s12951-025-03559-9 |
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