Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy
T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed o...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
|
| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523002733 |
| _version_ | 1827636280666619904 |
|---|---|
| author | Xiaodi Liu Qi Zhang Yixia Liang Shiyu Xiong Yan Cai Jincheng Cao Yanni Xu Xiaolin Xu Ye Wu Qiang Lu Xiaoding Xu Baoming Luo |
| author_facet | Xiaodi Liu Qi Zhang Yixia Liang Shiyu Xiong Yan Cai Jincheng Cao Yanni Xu Xiaolin Xu Ye Wu Qiang Lu Xiaoding Xu Baoming Luo |
| author_sort | Xiaodi Liu |
| collection | DOAJ |
| description | T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy. |
| first_indexed | 2024-03-09T15:40:48Z |
| format | Article |
| id | doaj.art-5c85d921d6d0445da6472fbb3838f530 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-09T15:40:48Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-5c85d921d6d0445da6472fbb3838f5302023-11-25T04:47:43ZengElsevierActa Pharmaceutica Sinica B2211-38352023-12-01131250485059Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapyXiaodi Liu0Qi Zhang1Yixia Liang2Shiyu Xiong3Yan Cai4Jincheng Cao5Yanni Xu6Xiaolin Xu7Ye Wu8Qiang Lu9Xiaoding Xu10Baoming Luo11Department of Ultrasound, Laboratory of Ultrasound Imaging and Drug, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Ultrasound, Central People's Hospital of Zhanjiang, Zhanjiang 524045, ChinaDepartment of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Ultrasound, Laboratory of Ultrasound Imaging and Drug, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Corresponding authors.Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Corresponding authors.T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.http://www.sciencedirect.com/science/article/pii/S2211383523002733NanoparticlesTumor-associated macrophagesMacrophage repolarizationT cell infiltrationT cell proliferationCancer immunotherapy |
| spellingShingle | Xiaodi Liu Qi Zhang Yixia Liang Shiyu Xiong Yan Cai Jincheng Cao Yanni Xu Xiaolin Xu Ye Wu Qiang Lu Xiaoding Xu Baoming Luo Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy Acta Pharmaceutica Sinica B Nanoparticles Tumor-associated macrophages Macrophage repolarization T cell infiltration T cell proliferation Cancer immunotherapy |
| title | Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy |
| title_full | Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy |
| title_fullStr | Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy |
| title_full_unstemmed | Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy |
| title_short | Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy |
| title_sort | nanoparticles nps mediated siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy |
| topic | Nanoparticles Tumor-associated macrophages Macrophage repolarization T cell infiltration T cell proliferation Cancer immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523002733 |
| work_keys_str_mv | AT xiaodiliu nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT qizhang nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT yixialiang nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT shiyuxiong nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT yancai nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT jinchengcao nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT yannixu nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT xiaolinxu nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT yewu nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT qianglu nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT xiaodingxu nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy AT baomingluo nanoparticlesnpsmediatedsiglec15silencingandmacrophagerepolarizationforenhancedcancerimmunotherapy |