Bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockade
Immune checkpoint blockade (ICB) therapy is a revolutionary approach to treat cancers, but still have limited clinical applications. Accumulating evidence pinpoints the immunosuppressive characteristics of the tumor microenvironment (TME) as one major obstacle. The TME, characterized by acidity, hyp...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2024-02-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X23003389 |
| _version_ | 1797450908584378368 |
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| author | Tianxu Fang Xiaona Cao Li Wang Mo Chen Yueyang Deng Guojun Chen |
| author_facet | Tianxu Fang Xiaona Cao Li Wang Mo Chen Yueyang Deng Guojun Chen |
| author_sort | Tianxu Fang |
| collection | DOAJ |
| description | Immune checkpoint blockade (ICB) therapy is a revolutionary approach to treat cancers, but still have limited clinical applications. Accumulating evidence pinpoints the immunosuppressive characteristics of the tumor microenvironment (TME) as one major obstacle. The TME, characterized by acidity, hypoxia and elevated ROS levels, exerts its detrimental effects on infiltrating anti-tumor immune cells. Here, we developed a TME-responsive and immunotherapeutic catalase-loaded calcium carbonate nanoparticles (termed as CAT@CaCO3 NPs) as the simple yet versatile multi-modulator for TME remodeling. CaCO3 NPs can consume protons in the acidic TME to normalize the TME pH. CAT catalyzed the decomposition of ROS and thus generated O2. The released Ca2+ led to Ca2+ overload in the tumor cells which then triggered the release of damage-associated molecular patterns (DAMP) signals to initiate anti-tumor immune responses, including tumor antigen presentation by dendritic cells. Meanwhile, CAT@CaCO3 NPs-induced immunosupportive TME also promoted the polarization of the M2 tumor-associated macrophages to the M1 phenotype, further enhancing tumor antigen presentation. Consequently, T cell-mediated anti-tumor responses were activated, the efficacy of which was further boosted by aPD-1 immune checkpoint blockade. Our study demonstrated that local treatment of CAT@CaCO3 NPs and aPD-1 combination can effectively evoke local and systemic anti-tumor immune responses, inhibiting the growth of treated tumors and distant diseases. |
| first_indexed | 2024-03-09T14:46:20Z |
| format | Article |
| id | doaj.art-4a8ae53638d04235adfd17c556109c1b |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-03-09T14:46:20Z |
| publishDate | 2024-02-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-4a8ae53638d04235adfd17c556109c1b2023-11-27T04:15:06ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-02-0132530542Bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockadeTianxu Fang0Xiaona Cao1Li Wang2Mo Chen3Yueyang Deng4Guojun Chen5Department of Biomedical Engineering, McGill University, Montreal, QC, H3G 0B1, Canada; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3G 0B1, CanadaDepartment of Biomedical Engineering, McGill University, Montreal, QC, H3G 0B1, Canada; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3G 0B1, CanadaDepartment of Biomedical Engineering, McGill University, Montreal, QC, H3G 0B1, Canada; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3G 0B1, CanadaDepartment of Biomedical Engineering, McGill University, Montreal, QC, H3G 0B1, Canada; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3G 0B1, CanadaDepartment of Biomedical Engineering, McGill University, Montreal, QC, H3G 0B1, Canada; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3G 0B1, CanadaDepartment of Biomedical Engineering, McGill University, Montreal, QC, H3G 0B1, Canada; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3G 0B1, Canada; Corresponding author. Department of Biomedical Engineering, McGill University, Montreal, QC, H3G 0B1, Canada.Immune checkpoint blockade (ICB) therapy is a revolutionary approach to treat cancers, but still have limited clinical applications. Accumulating evidence pinpoints the immunosuppressive characteristics of the tumor microenvironment (TME) as one major obstacle. The TME, characterized by acidity, hypoxia and elevated ROS levels, exerts its detrimental effects on infiltrating anti-tumor immune cells. Here, we developed a TME-responsive and immunotherapeutic catalase-loaded calcium carbonate nanoparticles (termed as CAT@CaCO3 NPs) as the simple yet versatile multi-modulator for TME remodeling. CaCO3 NPs can consume protons in the acidic TME to normalize the TME pH. CAT catalyzed the decomposition of ROS and thus generated O2. The released Ca2+ led to Ca2+ overload in the tumor cells which then triggered the release of damage-associated molecular patterns (DAMP) signals to initiate anti-tumor immune responses, including tumor antigen presentation by dendritic cells. Meanwhile, CAT@CaCO3 NPs-induced immunosupportive TME also promoted the polarization of the M2 tumor-associated macrophages to the M1 phenotype, further enhancing tumor antigen presentation. Consequently, T cell-mediated anti-tumor responses were activated, the efficacy of which was further boosted by aPD-1 immune checkpoint blockade. Our study demonstrated that local treatment of CAT@CaCO3 NPs and aPD-1 combination can effectively evoke local and systemic anti-tumor immune responses, inhibiting the growth of treated tumors and distant diseases.http://www.sciencedirect.com/science/article/pii/S2452199X23003389Tumor microenvironmentImmune modulationCalcium carbonate nanoparticlesCancer immunotherapyImmune checkpoint inhibitorDrug delivery |
| spellingShingle | Tianxu Fang Xiaona Cao Li Wang Mo Chen Yueyang Deng Guojun Chen Bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockade Bioactive Materials Tumor microenvironment Immune modulation Calcium carbonate nanoparticles Cancer immunotherapy Immune checkpoint inhibitor Drug delivery |
| title | Bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockade |
| title_full | Bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockade |
| title_fullStr | Bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockade |
| title_full_unstemmed | Bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockade |
| title_short | Bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockade |
| title_sort | bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockade |
| topic | Tumor microenvironment Immune modulation Calcium carbonate nanoparticles Cancer immunotherapy Immune checkpoint inhibitor Drug delivery |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X23003389 |
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