Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy
Abstract Breast cancer, the most prevalent malignancy among women, frequently exhibits high HER2 expression, making HER2 a critical therapeutic target. Traditional treatments combining the anti‐HER2 antibody trastuzumab with immunotherapy face limitations due to toxicity and tumor microenvironment i...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202410778 |
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| author | Changyong Guo Fei Gao Guoyuan Wu Jinqiu Li Chunquan Sheng Shipeng He Honggang Hu |
| author_facet | Changyong Guo Fei Gao Guoyuan Wu Jinqiu Li Chunquan Sheng Shipeng He Honggang Hu |
| author_sort | Changyong Guo |
| collection | DOAJ |
| description | Abstract Breast cancer, the most prevalent malignancy among women, frequently exhibits high HER2 expression, making HER2 a critical therapeutic target. Traditional treatments combining the anti‐HER2 antibody trastuzumab with immunotherapy face limitations due to toxicity and tumor microenvironment immunosuppression. This study introduces an innovative strategy combining HER2‐targeting peptides with the photosensitizer (PSs) pyropheophorbide‐a (Pha) via a gelatinase‐cleavable linker, forming self‐assembling nanoparticles. These nanoparticles actively target breast cancer cells and generate reactive oxygen species (ROS) under near‐infrared light, effectively degrading HER2 proteins. Upon internalization, the linker is cleaved, releasing Pha‐PLG and enhancing intracellular photodynamic therapy (PDT). The Pha‐PLG molecules self‐assemble into nanofibers, prolonging circulation, boosting immune induction, and activating CD8+ T cells, thus promoting a robust anti‐tumor immune response. In vivo, studies confirm superior biosafety, tumor targeting, and HER2 degradation, with increased cytotoxic T cell activity and improved antitumor immunity. This integrated strategy offers a promising new avenue for breast cancer treatment. |
| format | Article |
| id | doaj-art-8d5c00ea29574501a1e23c6458e76bad |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-8d5c00ea29574501a1e23c6458e76bad2025-01-13T15:29:43ZengWileyAdvanced Science2198-38442025-01-01122n/an/a10.1002/advs.202410778Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer ImmunotherapyChangyong Guo0Fei Gao1Guoyuan Wu2Jinqiu Li3Chunquan Sheng4Shipeng He5Honggang Hu6School of Medicine or Institute of Translational Medicine Shanghai Engineering Research Center of Organ Repair Shanghai University 99 Shangda Road Shanghai 200444 P. R. ChinaSchool of Medicine or Institute of Translational Medicine Shanghai Engineering Research Center of Organ Repair Shanghai University 99 Shangda Road Shanghai 200444 P. R. ChinaSchool of Medicine or Institute of Translational Medicine Shanghai Engineering Research Center of Organ Repair Shanghai University 99 Shangda Road Shanghai 200444 P. R. ChinaSchool of Medicine or Institute of Translational Medicine Shanghai Engineering Research Center of Organ Repair Shanghai University 99 Shangda Road Shanghai 200444 P. R. ChinaThe Center for Basic Research and Innovation of Medicine and Pharmacy (MOE) School of Pharmacy Second Military Medical University (Naval Medical University) 325 Guohe Road Shanghai 200433 P. R. ChinaSchool of Medicine or Institute of Translational Medicine Shanghai Engineering Research Center of Organ Repair Shanghai University 99 Shangda Road Shanghai 200444 P. R. ChinaSchool of Medicine or Institute of Translational Medicine Shanghai Engineering Research Center of Organ Repair Shanghai University 99 Shangda Road Shanghai 200444 P. R. ChinaAbstract Breast cancer, the most prevalent malignancy among women, frequently exhibits high HER2 expression, making HER2 a critical therapeutic target. Traditional treatments combining the anti‐HER2 antibody trastuzumab with immunotherapy face limitations due to toxicity and tumor microenvironment immunosuppression. This study introduces an innovative strategy combining HER2‐targeting peptides with the photosensitizer (PSs) pyropheophorbide‐a (Pha) via a gelatinase‐cleavable linker, forming self‐assembling nanoparticles. These nanoparticles actively target breast cancer cells and generate reactive oxygen species (ROS) under near‐infrared light, effectively degrading HER2 proteins. Upon internalization, the linker is cleaved, releasing Pha‐PLG and enhancing intracellular photodynamic therapy (PDT). The Pha‐PLG molecules self‐assemble into nanofibers, prolonging circulation, boosting immune induction, and activating CD8+ T cells, thus promoting a robust anti‐tumor immune response. In vivo, studies confirm superior biosafety, tumor targeting, and HER2 degradation, with increased cytotoxic T cell activity and improved antitumor immunity. This integrated strategy offers a promising new avenue for breast cancer treatment.https://doi.org/10.1002/advs.202410778breast cancergelatinase responsive peptidesimmune inductionphoto‐controlled her2 protein degradationphotodynamic immunotherapy |
| spellingShingle | Changyong Guo Fei Gao Guoyuan Wu Jinqiu Li Chunquan Sheng Shipeng He Honggang Hu Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy Advanced Science breast cancer gelatinase responsive peptides immune induction photo‐controlled her2 protein degradation photodynamic immunotherapy |
| title | Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy |
| title_full | Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy |
| title_fullStr | Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy |
| title_full_unstemmed | Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy |
| title_short | Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy |
| title_sort | precise her2 protein degradation via peptide conjugated photodynamic therapy for enhanced breast cancer immunotherapy |
| topic | breast cancer gelatinase responsive peptides immune induction photo‐controlled her2 protein degradation photodynamic immunotherapy |
| url | https://doi.org/10.1002/advs.202410778 |
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