An Immune‐Enhancing Injectable Hydrogel Loaded with Esketamine and DDP Promotes Painless Immunochemotherapy to Inhibit Breast Cancer Growth
Chemotherapy is the cornerstone of triple‐negative breast cancer. The poor effectiveness and severe neuropathic pain caused by it have a significant impact on the immune system. Studies confirmed that immune cells in the tumor microenvironment (TME), have critical roles in tumor immune regulation an...
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| creator | Yin, Xiali Ke, Yaohua Liang, Ying Zhang, Shuxian Chen, Ziqi Yu, Lixia Jiang, Ming Liu, Qin Gu, Xiaoping |
| description | Chemotherapy is the cornerstone of triple‐negative breast cancer. The poor effectiveness and severe neuropathic pain caused by it have a significant impact on the immune system. Studies confirmed that immune cells in the tumor microenvironment (TME), have critical roles in tumor immune regulation and prognosis. In this study, it is revealed that the painless administration of Esketamine, combined with Cisplatin (DDP), can exert an anti‐tumor effect, which is further boosted by the hydrogel delivery system. It is also discovered that Esketamine combined with DDP co‐loaded in Poloxamer Hydrogel (PDEH) induces local immunity by increasing mature Dendritic Cells (mDCs) and activated T cells in PDEH group while the regulatory T cells (Tregs) known as CD4+CD25+FoxP3+decreased significantly. Finally, , CD8+ and CD4+ T cells in the spleen exhibited a significant increase, suggesting a lasting immune impact of PDEH. This study proposes that Esketamine can serve as a painless immune modulator, enhancing an anti‐tumor effect while co‐loaded in poloxamer hydrogel with DDP. Along with improving immune cells in the microenvironment, it can potentially alleviate anxiety and depression. With its outstanding bio‐safety profile, it offers promising new possibilities for painless clinical therapy.
The analgesics currently employed in tumor are immunosuppressive. A painless administration of Esketamine combined with Cisplatin (DDP)co‐loaded in a thermo‐sensitive injectable hydrogel (PDEH) is designed to improve the immunosuppressive tumor microenvironment (TME) by activating Dendritic Cells (DCs), interferon‐γ (IFN‐γ) cells and inhibiting regulatory T cells (Tregs) on murine breast cancer. Furthermore, the anxiety and depression of mice are also relieved. |
| doi_str_mv | 10.1002/adhm.202401373 |
| format | Article |
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The analgesics currently employed in tumor are immunosuppressive. A painless administration of Esketamine combined with Cisplatin (DDP)co‐loaded in a thermo‐sensitive injectable hydrogel (PDEH) is designed to improve the immunosuppressive tumor microenvironment (TME) by activating Dendritic Cells (DCs), interferon‐γ (IFN‐γ) cells and inhibiting regulatory T cells (Tregs) on murine breast cancer. Furthermore, the anxiety and depression of mice are also relieved.</description><identifier>ISSN: 2192-2640</identifier><identifier>ISSN: 2192-2659</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202401373</identifier><identifier>PMID: 39118566</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject><![CDATA[Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Anxiety - complications ; Anxiety - drug therapy ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - immunology ; Breast Neoplasms - pathology ; Breast Neoplasms - psychology ; CD25 antigen ; CD4 antigen ; CD8 antigen ; Cell Growth Processes - drug effects ; Cell Line, Tumor ; Chemotherapy ; Cisplatin ; Cisplatin - administration & dosage ; Cisplatin - pharmacology ; Cisplatin - therapeutic use ; Dendritic cells ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Depression - complications ; Depression - drug therapy ; esketamine ; Female ; Foxp3 protein ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogels ; Hydrogels - administration & dosage ; Hydrogels - adverse effects ; Immune system ; Immunity, Innate - drug effects ; Immunoregulation ; Immunotherapy - methods ; injectable hydrogel ; Ketamine - administration & dosage ; Ketamine - pharmacology ; Ketamine - therapeutic use ; local immune ; Lymph Nodes - drug effects ; Lymph Nodes - immunology ; Lymphocytes ; Lymphocytes T ; Mice ; Mice, Inbred BALB C ; Neuralgia ; Pain - immunology ; Pain - prevention & control ; Pain - psychology ; Poloxamer - administration & dosage ; Poloxamer - adverse effects ; Poloxamers ; T-Lymphocytes, Regulatory - drug effects ; Tumor microenvironment ; Tumor Microenvironment - drug effects ; Tumors]]></subject><ispartof>Advanced healthcare materials, 2024-11, Vol.13 (29), p.e2401373-n/a</ispartof><rights>2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH</rights><rights>2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3543-9ef01719567361f0d42d3963297358fc08bc52708b6234a63c9ff0f12266a4503</cites><orcidid>0000-0002-3034-8396</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.202401373$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.202401373$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39118566$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yin, Xiali</creatorcontrib><creatorcontrib>Ke, Yaohua</creatorcontrib><creatorcontrib>Liang, Ying</creatorcontrib><creatorcontrib>Zhang, Shuxian</creatorcontrib><creatorcontrib>Chen, Ziqi</creatorcontrib><creatorcontrib>Yu, Lixia</creatorcontrib><creatorcontrib>Jiang, Ming</creatorcontrib><creatorcontrib>Liu, Qin</creatorcontrib><creatorcontrib>Gu, Xiaoping</creatorcontrib><title>An Immune‐Enhancing Injectable Hydrogel Loaded with Esketamine and DDP Promotes Painless Immunochemotherapy to Inhibit Breast Cancer Growth</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>Chemotherapy is the cornerstone of triple‐negative breast cancer. The poor effectiveness and severe neuropathic pain caused by it have a significant impact on the immune system. Studies confirmed that immune cells in the tumor microenvironment (TME), have critical roles in tumor immune regulation and prognosis. In this study, it is revealed that the painless administration of Esketamine, combined with Cisplatin (DDP), can exert an anti‐tumor effect, which is further boosted by the hydrogel delivery system. It is also discovered that Esketamine combined with DDP co‐loaded in Poloxamer Hydrogel (PDEH) induces local immunity by increasing mature Dendritic Cells (mDCs) and activated T cells in PDEH group while the regulatory T cells (Tregs) known as CD4+CD25+FoxP3+decreased significantly. Finally, , CD8+ and CD4+ T cells in the spleen exhibited a significant increase, suggesting a lasting immune impact of PDEH. This study proposes that Esketamine can serve as a painless immune modulator, enhancing an anti‐tumor effect while co‐loaded in poloxamer hydrogel with DDP. Along with improving immune cells in the microenvironment, it can potentially alleviate anxiety and depression. With its outstanding bio‐safety profile, it offers promising new possibilities for painless clinical therapy.
The analgesics currently employed in tumor are immunosuppressive. A painless administration of Esketamine combined with Cisplatin (DDP)co‐loaded in a thermo‐sensitive injectable hydrogel (PDEH) is designed to improve the immunosuppressive tumor microenvironment (TME) by activating Dendritic Cells (DCs), interferon‐γ (IFN‐γ) cells and inhibiting regulatory T cells (Tregs) on murine breast cancer. Furthermore, the anxiety and depression of mice are also relieved.</description><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Anxiety - complications</subject><subject>Anxiety - drug therapy</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - psychology</subject><subject>CD25 antigen</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell Growth Processes - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Cisplatin - administration & dosage</subject><subject>Cisplatin - pharmacology</subject><subject>Cisplatin - therapeutic use</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - 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immunology</subject><subject>Pain - prevention & control</subject><subject>Pain - psychology</subject><subject>Poloxamer - administration & dosage</subject><subject>Poloxamer - adverse effects</subject><subject>Poloxamers</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>Tumor microenvironment</subject><subject>Tumor Microenvironment - drug effects</subject><subject>Tumors</subject><issn>2192-2640</issn><issn>2192-2659</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNqFkcuO0zAUhiMEYkbDbFkiS2zYtPgSO_EKlbZMKxXRBawtNzlpXBK72M5U3fECSDzjPMl41KFcNnhzLPvzd3z0Z9lLgscEY_pW120_ppjmmLCCPckuKZF0RAWXT8_7HF9k1yHscFqCE1GS59kFk4SUXIjL7MfEomXfDxbuvv-c21bbytgtWtodVFFvOkCLY-3dFjq0crqGGh1MbNE8fIWoe2MBaVuj2WyN1t71LkJAa21sByGcvK5qIZ234PX-iKJL6tZsTETvPegQ0TR1BI9uvDvE9kX2rNFdgOvHepV9-TD_PF2MVp9ultPJalQxnrORhAaTgkguCiZIg-uc1kwKRmXBeNlUuNxUnBapCMpyLVglmwY3hFIhdM4xu8renbz7YdNDXYGNXndq702v_VE5bdTfN9a0autuFSG8pEmQDG8eDd59GyBE1ZtQQddpC24IimGJZS54kSf09T_ozg3epvkUIyzNQcucJ2p8oirvQvDQnH9DsHpIWz2krc5ppwev_pzhjP_KNgHyBBxMB8f_6NRktvj4W34PrWG3ow</recordid><startdate>20241101</startdate><enddate>20241101</enddate><creator>Yin, Xiali</creator><creator>Ke, Yaohua</creator><creator>Liang, Ying</creator><creator>Zhang, Shuxian</creator><creator>Chen, Ziqi</creator><creator>Yu, Lixia</creator><creator>Jiang, Ming</creator><creator>Liu, Qin</creator><creator>Gu, Xiaoping</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QP</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T5</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7TO</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3034-8396</orcidid></search><sort><creationdate>20241101</creationdate><title>An Immune‐Enhancing Injectable Hydrogel Loaded with Esketamine and DDP Promotes Painless Immunochemotherapy to Inhibit Breast Cancer Growth</title><author>Yin, Xiali ; Ke, Yaohua ; Liang, Ying ; Zhang, Shuxian ; Chen, Ziqi ; Yu, Lixia ; Jiang, Ming ; Liu, Qin ; Gu, Xiaoping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3543-9ef01719567361f0d42d3963297358fc08bc52708b6234a63c9ff0f12266a4503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - 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The poor effectiveness and severe neuropathic pain caused by it have a significant impact on the immune system. Studies confirmed that immune cells in the tumor microenvironment (TME), have critical roles in tumor immune regulation and prognosis. In this study, it is revealed that the painless administration of Esketamine, combined with Cisplatin (DDP), can exert an anti‐tumor effect, which is further boosted by the hydrogel delivery system. It is also discovered that Esketamine combined with DDP co‐loaded in Poloxamer Hydrogel (PDEH) induces local immunity by increasing mature Dendritic Cells (mDCs) and activated T cells in PDEH group while the regulatory T cells (Tregs) known as CD4+CD25+FoxP3+decreased significantly. Finally, , CD8+ and CD4+ T cells in the spleen exhibited a significant increase, suggesting a lasting immune impact of PDEH. This study proposes that Esketamine can serve as a painless immune modulator, enhancing an anti‐tumor effect while co‐loaded in poloxamer hydrogel with DDP. Along with improving immune cells in the microenvironment, it can potentially alleviate anxiety and depression. With its outstanding bio‐safety profile, it offers promising new possibilities for painless clinical therapy.
The analgesics currently employed in tumor are immunosuppressive. A painless administration of Esketamine combined with Cisplatin (DDP)co‐loaded in a thermo‐sensitive injectable hydrogel (PDEH) is designed to improve the immunosuppressive tumor microenvironment (TME) by activating Dendritic Cells (DCs), interferon‐γ (IFN‐γ) cells and inhibiting regulatory T cells (Tregs) on murine breast cancer. Furthermore, the anxiety and depression of mice are also relieved.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39118566</pmid><doi>10.1002/adhm.202401373</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-3034-8396</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Anxiety - complications Anxiety - drug therapy Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - immunology Breast Neoplasms - pathology Breast Neoplasms - psychology CD25 antigen CD4 antigen CD8 antigen Cell Growth Processes - drug effects Cell Line, Tumor Chemotherapy Cisplatin Cisplatin - administration & dosage Cisplatin - pharmacology Cisplatin - therapeutic use Dendritic cells Dendritic Cells - drug effects Dendritic Cells - immunology Depression - complications Depression - drug therapy esketamine Female Foxp3 protein Human Umbilical Vein Endothelial Cells Humans Hydrogels Hydrogels - administration & dosage Hydrogels - adverse effects Immune system Immunity, Innate - drug effects Immunoregulation Immunotherapy - methods injectable hydrogel Ketamine - administration & dosage Ketamine - pharmacology Ketamine - therapeutic use local immune Lymph Nodes - drug effects Lymph Nodes - immunology Lymphocytes Lymphocytes T Mice Mice, Inbred BALB C Neuralgia Pain - immunology Pain - prevention & control Pain - psychology Poloxamer - administration & dosage Poloxamer - adverse effects Poloxamers T-Lymphocytes, Regulatory - drug effects Tumor microenvironment Tumor Microenvironment - drug effects Tumors |
| title | An Immune‐Enhancing Injectable Hydrogel Loaded with Esketamine and DDP Promotes Painless Immunochemotherapy to Inhibit Breast Cancer Growth |
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