Decitabine/paclitaxel co-delivery systems modified with anti-PD-L1 antibodies mediate chemoimmunotherapy for Triple negative breast cancer
Triple-negative breast cancer (TNBC) is one of the major clinical problems to be solved urgently, because of its high malignancy, poor targeted therapy effect and easy occurrence of drug resistance and metastasis. Here, methyltransferase DNMT1 was identified as a key factor mediating PTX resistance...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Materials & Design |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127523009784 |
| _version_ | 1797347811593814016 |
|---|---|
| author | Yang He Qin Hu Liting Wang Chuanrong Chen |
| author_facet | Yang He Qin Hu Liting Wang Chuanrong Chen |
| author_sort | Yang He |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) is one of the major clinical problems to be solved urgently, because of its high malignancy, poor targeted therapy effect and easy occurrence of drug resistance and metastasis. Here, methyltransferase DNMT1 was identified as a key factor mediating PTX resistance for TNBC. Decitabine (DEC), an inhibitor of DNMT1, can inhibit the proliferation and metastasis of TNBC cells and reverse PTX resistance. In this study, we reported a new delivery system (DEC/PTX NPs@αPD-L1) co-loaded with DEC and PTX modified by anti-PD-L1 monoclonal antibody (αPD-L1), which can overcome drug resistance and metastasis through multi-mode synergistic effect. αPD-L1 increases the enrichment of nanoparticles in tumor tissue through active targeting effect, and blocks PD-L1 on the surface of TNBC cells, thereby activating anti-tumor immune while enhancing internalization of nanoparticles by tumor cells. Inside tumor cells, DEC inhibits EMT process and cancer stem cells to overcome PTX resistance and metastasis. PTX can not only exerts direct tumor killing effect, but also inhibit Treg cells from remodeling immune microenvironment, and induces efficient immunogenic death in cooperation with DEC. This delivery system, realizing tumor-specific synchronized chemoimmunotherapy, represents a promising therapeutic platform for TNBC. |
| first_indexed | 2024-03-08T11:54:20Z |
| format | Article |
| id | doaj.art-545fcd8f3ad84253aa856cc228830ee1 |
| institution | Directory Open Access Journal |
| issn | 0264-1275 |
| language | English |
| last_indexed | 2024-03-08T11:54:20Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj.art-545fcd8f3ad84253aa856cc228830ee12024-01-24T05:16:24ZengElsevierMaterials & Design0264-12752024-01-01237112562Decitabine/paclitaxel co-delivery systems modified with anti-PD-L1 antibodies mediate chemoimmunotherapy for Triple negative breast cancerYang He0Qin Hu1Liting Wang2Chuanrong Chen3Department of Oncology, Yijishan Hospital of Wannan Medical College, Wuhu 240001, ChinaDepartment of Oncology, Wuhu Hospital Affiliated to East China Normal University, Wuhu 240001, ChinaHouston Methodist Cancer Center/Weill Cornell Medicine, Houston, TX 77030, USADepartment of Oncology, Yijishan Hospital of Wannan Medical College, Wuhu 240001, China; Corresponding author.Triple-negative breast cancer (TNBC) is one of the major clinical problems to be solved urgently, because of its high malignancy, poor targeted therapy effect and easy occurrence of drug resistance and metastasis. Here, methyltransferase DNMT1 was identified as a key factor mediating PTX resistance for TNBC. Decitabine (DEC), an inhibitor of DNMT1, can inhibit the proliferation and metastasis of TNBC cells and reverse PTX resistance. In this study, we reported a new delivery system (DEC/PTX NPs@αPD-L1) co-loaded with DEC and PTX modified by anti-PD-L1 monoclonal antibody (αPD-L1), which can overcome drug resistance and metastasis through multi-mode synergistic effect. αPD-L1 increases the enrichment of nanoparticles in tumor tissue through active targeting effect, and blocks PD-L1 on the surface of TNBC cells, thereby activating anti-tumor immune while enhancing internalization of nanoparticles by tumor cells. Inside tumor cells, DEC inhibits EMT process and cancer stem cells to overcome PTX resistance and metastasis. PTX can not only exerts direct tumor killing effect, but also inhibit Treg cells from remodeling immune microenvironment, and induces efficient immunogenic death in cooperation with DEC. This delivery system, realizing tumor-specific synchronized chemoimmunotherapy, represents a promising therapeutic platform for TNBC.http://www.sciencedirect.com/science/article/pii/S0264127523009784DNMT1ImmunotherapyPD-L1Co-deliveryImmunogenic cell death |
| spellingShingle | Yang He Qin Hu Liting Wang Chuanrong Chen Decitabine/paclitaxel co-delivery systems modified with anti-PD-L1 antibodies mediate chemoimmunotherapy for Triple negative breast cancer Materials & Design DNMT1 Immunotherapy PD-L1 Co-delivery Immunogenic cell death |
| title | Decitabine/paclitaxel co-delivery systems modified with anti-PD-L1 antibodies mediate chemoimmunotherapy for Triple negative breast cancer |
| title_full | Decitabine/paclitaxel co-delivery systems modified with anti-PD-L1 antibodies mediate chemoimmunotherapy for Triple negative breast cancer |
| title_fullStr | Decitabine/paclitaxel co-delivery systems modified with anti-PD-L1 antibodies mediate chemoimmunotherapy for Triple negative breast cancer |
| title_full_unstemmed | Decitabine/paclitaxel co-delivery systems modified with anti-PD-L1 antibodies mediate chemoimmunotherapy for Triple negative breast cancer |
| title_short | Decitabine/paclitaxel co-delivery systems modified with anti-PD-L1 antibodies mediate chemoimmunotherapy for Triple negative breast cancer |
| title_sort | decitabine paclitaxel co delivery systems modified with anti pd l1 antibodies mediate chemoimmunotherapy for triple negative breast cancer |
| topic | DNMT1 Immunotherapy PD-L1 Co-delivery Immunogenic cell death |
| url | http://www.sciencedirect.com/science/article/pii/S0264127523009784 |
| work_keys_str_mv | AT yanghe decitabinepaclitaxelcodeliverysystemsmodifiedwithantipdl1antibodiesmediatechemoimmunotherapyfortriplenegativebreastcancer AT qinhu decitabinepaclitaxelcodeliverysystemsmodifiedwithantipdl1antibodiesmediatechemoimmunotherapyfortriplenegativebreastcancer AT litingwang decitabinepaclitaxelcodeliverysystemsmodifiedwithantipdl1antibodiesmediatechemoimmunotherapyfortriplenegativebreastcancer AT chuanrongchen decitabinepaclitaxelcodeliverysystemsmodifiedwithantipdl1antibodiesmediatechemoimmunotherapyfortriplenegativebreastcancer |