Tumor Microenvironment‐Activated Nanocomposite for Self‐Amplifying Chemodynamic/Starvation Therapy Enhanced IDO‐Blockade Tumor Immunotherapy
Abstract Disrupting intracellular redox homeostasis combined with immune checkpoint blockade therapy is considered as an effective way to accelerate tumor cell death. However, suppressed tumor immune microenvironment and lower cargo delivery restrict the efficiency of tumor therapy. In this study, a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202303580 |
| _version_ | 1797401800230305792 |
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| author | Yulong Bian Bin Liu Binbin Ding Meifang Wang Meng Yuan Ping'an Ma Jun Lin |
| author_facet | Yulong Bian Bin Liu Binbin Ding Meifang Wang Meng Yuan Ping'an Ma Jun Lin |
| author_sort | Yulong Bian |
| collection | DOAJ |
| description | Abstract Disrupting intracellular redox homeostasis combined with immune checkpoint blockade therapy is considered as an effective way to accelerate tumor cell death. However, suppressed tumor immune microenvironment and lower cargo delivery restrict the efficiency of tumor therapy. In this study, a multifunctional tumor microenvironment (TME)‐responsive nanocomposite is constructed using manganese tetroxide (Mn3O4)‐decorated disulfide‐bond‐incorporated dendritic mesoporous organosilica nanoparticles (DMONs) to co‐deliver indoleamine 2,3‐dioxygenase (IDO) inhibitor Epacadostat (IDOi) and glucose oxidase (GOx) following modification with polyethylene glycol. Owing to the responsiveness of Mn3O4‐decorated DMONs to the mildly acidic and glutathione (GSH) overexpressed TME, the nanocomposite can rapidly decompose and release inner contents, thus substantially improving the cargo release ability. Mn3O4 can effectively catalyze hydrogen peroxide (H2O2) decomposition to generate oxygen, enhance the ability of GOx to consume glucose to produce H2O2, and further promote the generation of hydroxyl radicals (•OH) by Mn2+. Furthermore, Mn2+‐mediated GSH depletion and the production of •OH can disrupt intracellular redox homeostasis, contributing to immunogenic cell death. Simultaneously, IDOi can inhibit IDO to reverse inhibited immune response. The results show that self‐amplifying chemodynamic/starvation therapy combined IDO‐blockade immunotherapy synergistically inhibits tumor growth and metastasis in vivo. |
| first_indexed | 2024-03-09T02:16:31Z |
| format | Article |
| id | doaj.art-17f54dbb48b64022a1cad3ce85f458a2 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-09T02:16:31Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-17f54dbb48b64022a1cad3ce85f458a22023-12-07T04:08:35ZengWileyAdvanced Science2198-38442023-12-011034n/an/a10.1002/advs.202303580Tumor Microenvironment‐Activated Nanocomposite for Self‐Amplifying Chemodynamic/Starvation Therapy Enhanced IDO‐Blockade Tumor ImmunotherapyYulong Bian0Bin Liu1Binbin Ding2Meifang Wang3Meng Yuan4Ping'an Ma5Jun Lin6State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 ChinaState Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 ChinaState Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 ChinaState Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 ChinaState Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 ChinaState Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 ChinaState Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 ChinaAbstract Disrupting intracellular redox homeostasis combined with immune checkpoint blockade therapy is considered as an effective way to accelerate tumor cell death. However, suppressed tumor immune microenvironment and lower cargo delivery restrict the efficiency of tumor therapy. In this study, a multifunctional tumor microenvironment (TME)‐responsive nanocomposite is constructed using manganese tetroxide (Mn3O4)‐decorated disulfide‐bond‐incorporated dendritic mesoporous organosilica nanoparticles (DMONs) to co‐deliver indoleamine 2,3‐dioxygenase (IDO) inhibitor Epacadostat (IDOi) and glucose oxidase (GOx) following modification with polyethylene glycol. Owing to the responsiveness of Mn3O4‐decorated DMONs to the mildly acidic and glutathione (GSH) overexpressed TME, the nanocomposite can rapidly decompose and release inner contents, thus substantially improving the cargo release ability. Mn3O4 can effectively catalyze hydrogen peroxide (H2O2) decomposition to generate oxygen, enhance the ability of GOx to consume glucose to produce H2O2, and further promote the generation of hydroxyl radicals (•OH) by Mn2+. Furthermore, Mn2+‐mediated GSH depletion and the production of •OH can disrupt intracellular redox homeostasis, contributing to immunogenic cell death. Simultaneously, IDOi can inhibit IDO to reverse inhibited immune response. The results show that self‐amplifying chemodynamic/starvation therapy combined IDO‐blockade immunotherapy synergistically inhibits tumor growth and metastasis in vivo.https://doi.org/10.1002/advs.202303580chemodynamic/starvation therapyimmunogenic cell deathimmunotherapyindoleamine 2,3‐dioxygenasetumor microenvironment‐responsive |
| spellingShingle | Yulong Bian Bin Liu Binbin Ding Meifang Wang Meng Yuan Ping'an Ma Jun Lin Tumor Microenvironment‐Activated Nanocomposite for Self‐Amplifying Chemodynamic/Starvation Therapy Enhanced IDO‐Blockade Tumor Immunotherapy Advanced Science chemodynamic/starvation therapy immunogenic cell death immunotherapy indoleamine 2,3‐dioxygenase tumor microenvironment‐responsive |
| title | Tumor Microenvironment‐Activated Nanocomposite for Self‐Amplifying Chemodynamic/Starvation Therapy Enhanced IDO‐Blockade Tumor Immunotherapy |
| title_full | Tumor Microenvironment‐Activated Nanocomposite for Self‐Amplifying Chemodynamic/Starvation Therapy Enhanced IDO‐Blockade Tumor Immunotherapy |
| title_fullStr | Tumor Microenvironment‐Activated Nanocomposite for Self‐Amplifying Chemodynamic/Starvation Therapy Enhanced IDO‐Blockade Tumor Immunotherapy |
| title_full_unstemmed | Tumor Microenvironment‐Activated Nanocomposite for Self‐Amplifying Chemodynamic/Starvation Therapy Enhanced IDO‐Blockade Tumor Immunotherapy |
| title_short | Tumor Microenvironment‐Activated Nanocomposite for Self‐Amplifying Chemodynamic/Starvation Therapy Enhanced IDO‐Blockade Tumor Immunotherapy |
| title_sort | tumor microenvironment activated nanocomposite for self amplifying chemodynamic starvation therapy enhanced ido blockade tumor immunotherapy |
| topic | chemodynamic/starvation therapy immunogenic cell death immunotherapy indoleamine 2,3‐dioxygenase tumor microenvironment‐responsive |
| url | https://doi.org/10.1002/advs.202303580 |
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