Injectable Polypeptide Hydrogel Depots Containing Dual Immune Checkpoint Inhibitors and Doxorubicin for Improved Tumor Immunotherapy and Post-Surgical Tumor Treatment
In this work, we developed a strategy for local chemo-immunotherapy through simultaneous incorporation of dual immune checkpoint blockade (ICB) antibodies, anti-cytotoxic T-lymphocyte-associated protein 4 (aCTLA-4) and anti-programmed cell death protein 1 (aPD-1), and a chemotherapy drug, doxorubici...
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| Materyal Türü: | Makale |
| Dil: | English |
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MDPI AG
2023-01-01
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| Seri Bilgileri: | Pharmaceutics |
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| Online Erişim: | https://www.mdpi.com/1999-4923/15/2/428 |
| _version_ | 1827755959902011392 |
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| author | Zhixiong Chen Yan Rong Junfeng Ding Xueliang Cheng Xuesi Chen Chaoliang He |
| author_facet | Zhixiong Chen Yan Rong Junfeng Ding Xueliang Cheng Xuesi Chen Chaoliang He |
| author_sort | Zhixiong Chen |
| collection | DOAJ |
| description | In this work, we developed a strategy for local chemo-immunotherapy through simultaneous incorporation of dual immune checkpoint blockade (ICB) antibodies, anti-cytotoxic T-lymphocyte-associated protein 4 (aCTLA-4) and anti-programmed cell death protein 1 (aPD-1), and a chemotherapy drug, doxorubicin (Dox), into a thermo-gelling polypeptide hydrogel. The hydrogel encapsulating Dox or IgG model antibody showed sustained release profiles for more than 12 days in vitro, and the drug release and hydrogel degradation were accelerated in the presence of enzymes. In comparison to free drug solutions or hydrogels containing Dox or antibodies only, the Dox/aCTLA-4/aPD-1 co-loaded hydrogel achieved improved tumor suppression efficiency, strengthened antitumor immune response, and prolonged animal survival time after peritumoral injection into mice bearing B16F10 melanoma. Additionally, after injection of Dox/aCTLA-4/aPD-1 co-loaded hydrogel into the surgical site following tumor resection, a significantly enhanced inhibition on tumor reoccurrence was demonstrated. Thus, the polypeptide hydrogel-based chemo-immunotherapy strategy has potential in anti-tumor therapy and the prevention of tumor reoccurrence. |
| first_indexed | 2024-03-11T08:17:28Z |
| format | Article |
| id | doaj.art-ed4a2ec7fd224e01bfe7dc85a0bf37ab |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:17:28Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ed4a2ec7fd224e01bfe7dc85a0bf37ab2023-11-16T22:39:48ZengMDPI AGPharmaceutics1999-49232023-01-0115242810.3390/pharmaceutics15020428Injectable Polypeptide Hydrogel Depots Containing Dual Immune Checkpoint Inhibitors and Doxorubicin for Improved Tumor Immunotherapy and Post-Surgical Tumor TreatmentZhixiong Chen0Yan Rong1Junfeng Ding2Xueliang Cheng3Xuesi Chen4Chaoliang He5CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaCAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaCAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaCAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaCAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaCAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaIn this work, we developed a strategy for local chemo-immunotherapy through simultaneous incorporation of dual immune checkpoint blockade (ICB) antibodies, anti-cytotoxic T-lymphocyte-associated protein 4 (aCTLA-4) and anti-programmed cell death protein 1 (aPD-1), and a chemotherapy drug, doxorubicin (Dox), into a thermo-gelling polypeptide hydrogel. The hydrogel encapsulating Dox or IgG model antibody showed sustained release profiles for more than 12 days in vitro, and the drug release and hydrogel degradation were accelerated in the presence of enzymes. In comparison to free drug solutions or hydrogels containing Dox or antibodies only, the Dox/aCTLA-4/aPD-1 co-loaded hydrogel achieved improved tumor suppression efficiency, strengthened antitumor immune response, and prolonged animal survival time after peritumoral injection into mice bearing B16F10 melanoma. Additionally, after injection of Dox/aCTLA-4/aPD-1 co-loaded hydrogel into the surgical site following tumor resection, a significantly enhanced inhibition on tumor reoccurrence was demonstrated. Thus, the polypeptide hydrogel-based chemo-immunotherapy strategy has potential in anti-tumor therapy and the prevention of tumor reoccurrence.https://www.mdpi.com/1999-4923/15/2/428hydrogelcombination therapyimmunotherapypolypeptideICB therapy |
| spellingShingle | Zhixiong Chen Yan Rong Junfeng Ding Xueliang Cheng Xuesi Chen Chaoliang He Injectable Polypeptide Hydrogel Depots Containing Dual Immune Checkpoint Inhibitors and Doxorubicin for Improved Tumor Immunotherapy and Post-Surgical Tumor Treatment Pharmaceutics hydrogel combination therapy immunotherapy polypeptide ICB therapy |
| title | Injectable Polypeptide Hydrogel Depots Containing Dual Immune Checkpoint Inhibitors and Doxorubicin for Improved Tumor Immunotherapy and Post-Surgical Tumor Treatment |
| title_full | Injectable Polypeptide Hydrogel Depots Containing Dual Immune Checkpoint Inhibitors and Doxorubicin for Improved Tumor Immunotherapy and Post-Surgical Tumor Treatment |
| title_fullStr | Injectable Polypeptide Hydrogel Depots Containing Dual Immune Checkpoint Inhibitors and Doxorubicin for Improved Tumor Immunotherapy and Post-Surgical Tumor Treatment |
| title_full_unstemmed | Injectable Polypeptide Hydrogel Depots Containing Dual Immune Checkpoint Inhibitors and Doxorubicin for Improved Tumor Immunotherapy and Post-Surgical Tumor Treatment |
| title_short | Injectable Polypeptide Hydrogel Depots Containing Dual Immune Checkpoint Inhibitors and Doxorubicin for Improved Tumor Immunotherapy and Post-Surgical Tumor Treatment |
| title_sort | injectable polypeptide hydrogel depots containing dual immune checkpoint inhibitors and doxorubicin for improved tumor immunotherapy and post surgical tumor treatment |
| topic | hydrogel combination therapy immunotherapy polypeptide ICB therapy |
| url | https://www.mdpi.com/1999-4923/15/2/428 |
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