Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer
Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin (DOX) and Toll-like receptor 7 agonist imiquimod (IMQ) in low molecular weight heparin (LMWH)-d-α-tocopheryl succinate (TOS) micel...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-07-01
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| Series: | Acta Pharmaceutica Sinica B |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383518309663 |
| _version_ | 1818447434926260224 |
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| author | Jiaojie Wei Yang Long Rong Guo Xinlei Liu Xian Tang Jingdong Rao Sheng Yin Zhirong Zhang Man Li Qin He |
| author_facet | Jiaojie Wei Yang Long Rong Guo Xinlei Liu Xian Tang Jingdong Rao Sheng Yin Zhirong Zhang Man Li Qin He |
| author_sort | Jiaojie Wei |
| collection | DOAJ |
| description | Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin (DOX) and Toll-like receptor 7 agonist imiquimod (IMQ) in low molecular weight heparin (LMWH)-d-α-tocopheryl succinate (TOS) micelles (LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles (LT-DOX) generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles (LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1 (PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8+ CTLs/Treg and CD4+ Teff/Treg. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer. KEY WORDS: Checkpoint blockade, Immunotherapy, Immunogenic cell death, Anti-metastasis, Nanoparticle |
| first_indexed | 2024-12-14T20:03:34Z |
| format | Article |
| id | doaj.art-062830608b654b78a9b1152530016de0 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-14T20:03:34Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-062830608b654b78a9b1152530016de02022-12-21T22:49:06ZengElsevierActa Pharmaceutica Sinica B2211-38352019-07-0194819831Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancerJiaojie Wei0Yang Long1Rong Guo2Xinlei Liu3Xian Tang4Jingdong Rao5Sheng Yin6Zhirong Zhang7Man Li8Qin He9Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaCorresponding author.; Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaImmunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin (DOX) and Toll-like receptor 7 agonist imiquimod (IMQ) in low molecular weight heparin (LMWH)-d-α-tocopheryl succinate (TOS) micelles (LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles (LT-DOX) generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles (LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1 (PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8+ CTLs/Treg and CD4+ Teff/Treg. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer. KEY WORDS: Checkpoint blockade, Immunotherapy, Immunogenic cell death, Anti-metastasis, Nanoparticlehttp://www.sciencedirect.com/science/article/pii/S2211383518309663 |
| spellingShingle | Jiaojie Wei Yang Long Rong Guo Xinlei Liu Xian Tang Jingdong Rao Sheng Yin Zhirong Zhang Man Li Qin He Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer Acta Pharmaceutica Sinica B |
| title | Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer |
| title_full | Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer |
| title_fullStr | Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer |
| title_full_unstemmed | Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer |
| title_short | Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer |
| title_sort | multifunctional polymeric micelle based chemo immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211383518309663 |
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