Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles
Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or a...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
|
| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523001107 |
| _version_ | 1797690240578617344 |
|---|---|
| author | Mei Lu Haonan Xing Wanxuan Shao Pengfei Wu Yuchuan Fan Huining He Stefan Barth Aiping Zheng Xing-Jie Liang Yuanyu Huang |
| author_facet | Mei Lu Haonan Xing Wanxuan Shao Pengfei Wu Yuchuan Fan Huining He Stefan Barth Aiping Zheng Xing-Jie Liang Yuanyu Huang |
| author_sort | Mei Lu |
| collection | DOAJ |
| description | Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy. |
| first_indexed | 2024-03-12T01:56:42Z |
| format | Article |
| id | doaj.art-f3a9f81567984c40a01202e52b271d53 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-12T01:56:42Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-f3a9f81567984c40a01202e52b271d532023-09-08T04:33:17ZengElsevierActa Pharmaceutica Sinica B2211-38352023-09-0113939453955Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesiclesMei Lu0Haonan Xing1Wanxuan Shao2Pengfei Wu3Yuchuan Fan4Huining He5Stefan Barth6Aiping Zheng7Xing-Jie Liang8Yuanyu Huang9Advanced Research Institute of Multidisciplinary Science, School of Life Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, China; Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, ChinaChinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaAdvanced Research Institute of Multidisciplinary Science, School of Life Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, ChinaAdvanced Research Institute of Multidisciplinary Science, School of Life Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, ChinaAdvanced Research Institute of Multidisciplinary Science, School of Life Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, ChinaTianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, ChinaSouth African Research Chair in Cancer Biotechnology, Institute of Infectious Disease and Molecular Medicine (IDM), Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaChinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China; Corresponding authors.Advanced Research Institute of Multidisciplinary Science, School of Life Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, China; Corresponding authors.Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.http://www.sciencedirect.com/science/article/pii/S2211383523001107Antitumor synergismCombined cancer immunotherapyp21-activated kinase 4RNA interferenceImmunogenic phototherapyExtracellular vesicles |
| spellingShingle | Mei Lu Haonan Xing Wanxuan Shao Pengfei Wu Yuchuan Fan Huining He Stefan Barth Aiping Zheng Xing-Jie Liang Yuanyu Huang Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles Acta Pharmaceutica Sinica B Antitumor synergism Combined cancer immunotherapy p21-activated kinase 4 RNA interference Immunogenic phototherapy Extracellular vesicles |
| title | Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles |
| title_full | Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles |
| title_fullStr | Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles |
| title_full_unstemmed | Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles |
| title_short | Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles |
| title_sort | antitumor synergism between pak4 silencing and immunogenic phototherapy of engineered extracellular vesicles |
| topic | Antitumor synergism Combined cancer immunotherapy p21-activated kinase 4 RNA interference Immunogenic phototherapy Extracellular vesicles |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523001107 |
| work_keys_str_mv | AT meilu antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles AT haonanxing antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles AT wanxuanshao antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles AT pengfeiwu antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles AT yuchuanfan antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles AT huininghe antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles AT stefanbarth antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles AT aipingzheng antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles AT xingjieliang antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles AT yuanyuhuang antitumorsynergismbetweenpak4silencingandimmunogenicphototherapyofengineeredextracellularvesicles |