Nanodelivery of scutellarin induces immunogenic cell death for treating hepatocellular carcinoma
[Display omitted] Hepatocellular carcinoma (HCC) causes the immunosuppressive tumor microenvironment (TME) resistant to current immunotherapy. The immunogenic apoptosis (currently termed immunogenic cell death, ICD) of cancer cells may induce the adaptive immunity against tumors, thereby providing g...
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| Veröffentlicht in: | International journal of pharmaceutics 2023-07, Vol.642, p.123114-123114, Article 123114 |
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| container_title | International journal of pharmaceutics |
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| creator | Li, Linlin Zou, Yifang Wang, Lingzhi Yang, Leilei Li, Yutong Liao, Anqi Chen, Zheng Yu, Zhuo Guo, Jianfeng Han, Shulan |
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Hepatocellular carcinoma (HCC) causes the immunosuppressive tumor microenvironment (TME) resistant to current immunotherapy. The immunogenic apoptosis (currently termed immunogenic cell death, ICD) of cancer cells may induce the adaptive immunity against tumors, thereby providing great potential for treating HCC. In this study, we have confirmed the potential of scutellarin (SCU, a flavonoid found in Erigeron breviscapus) for triggering ICD in HCC cells. To facilitate in vivo application of SCU for HCC immunotherapy, an aminoethyl anisamide-targeted polyethylene glycol-modified poly(lactide-co-glycolide) (PLGA-PEG-AEAA) was produced to facilitate SCU delivery in this study. The resultant nanoformulation (PLGA-PEG-AEAA.SCU) remarkably promoted blood circulation and tumor delivery in the orthotopic HCC mouse model. Consequently, PLGA-PEG-AEAA.SCU reversed the immune suppressive TME and achieved the immunotherapeutic efficacy, resulting in significantly longer survival of mice, without inducing toxicity. These findings uncover the ICD potential of SCU and provide a promising strategy for HCC immunotherapy. |
| doi_str_mv | 10.1016/j.ijpharm.2023.123114 |
| format | Article |
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Hepatocellular carcinoma (HCC) causes the immunosuppressive tumor microenvironment (TME) resistant to current immunotherapy. The immunogenic apoptosis (currently termed immunogenic cell death, ICD) of cancer cells may induce the adaptive immunity against tumors, thereby providing great potential for treating HCC. In this study, we have confirmed the potential of scutellarin (SCU, a flavonoid found in Erigeron breviscapus) for triggering ICD in HCC cells. To facilitate in vivo application of SCU for HCC immunotherapy, an aminoethyl anisamide-targeted polyethylene glycol-modified poly(lactide-co-glycolide) (PLGA-PEG-AEAA) was produced to facilitate SCU delivery in this study. The resultant nanoformulation (PLGA-PEG-AEAA.SCU) remarkably promoted blood circulation and tumor delivery in the orthotopic HCC mouse model. Consequently, PLGA-PEG-AEAA.SCU reversed the immune suppressive TME and achieved the immunotherapeutic efficacy, resulting in significantly longer survival of mice, without inducing toxicity. These findings uncover the ICD potential of SCU and provide a promising strategy for HCC immunotherapy.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2023.123114</identifier><identifier>PMID: 37301243</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Apigenin ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - metabolism ; Drug delivery ; Immunogenic Cell Death ; Immunotherapy ; Liver cancer ; Liver Neoplasms - drug therapy ; Liver Neoplasms - metabolism ; Mice ; Nanoparticle ; Tumor Microenvironment</subject><ispartof>International journal of pharmaceutics, 2023-07, Vol.642, p.123114-123114, Article 123114</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-4f738447a6d6191c8676d3917697342daee6d0e21aba438f4779a2bf208397773</citedby><cites>FETCH-LOGICAL-c365t-4f738447a6d6191c8676d3917697342daee6d0e21aba438f4779a2bf208397773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijpharm.2023.123114$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37301243$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Linlin</creatorcontrib><creatorcontrib>Zou, Yifang</creatorcontrib><creatorcontrib>Wang, Lingzhi</creatorcontrib><creatorcontrib>Yang, Leilei</creatorcontrib><creatorcontrib>Li, Yutong</creatorcontrib><creatorcontrib>Liao, Anqi</creatorcontrib><creatorcontrib>Chen, Zheng</creatorcontrib><creatorcontrib>Yu, Zhuo</creatorcontrib><creatorcontrib>Guo, Jianfeng</creatorcontrib><creatorcontrib>Han, Shulan</creatorcontrib><title>Nanodelivery of scutellarin induces immunogenic cell death for treating hepatocellular carcinoma</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
Hepatocellular carcinoma (HCC) causes the immunosuppressive tumor microenvironment (TME) resistant to current immunotherapy. The immunogenic apoptosis (currently termed immunogenic cell death, ICD) of cancer cells may induce the adaptive immunity against tumors, thereby providing great potential for treating HCC. In this study, we have confirmed the potential of scutellarin (SCU, a flavonoid found in Erigeron breviscapus) for triggering ICD in HCC cells. To facilitate in vivo application of SCU for HCC immunotherapy, an aminoethyl anisamide-targeted polyethylene glycol-modified poly(lactide-co-glycolide) (PLGA-PEG-AEAA) was produced to facilitate SCU delivery in this study. The resultant nanoformulation (PLGA-PEG-AEAA.SCU) remarkably promoted blood circulation and tumor delivery in the orthotopic HCC mouse model. Consequently, PLGA-PEG-AEAA.SCU reversed the immune suppressive TME and achieved the immunotherapeutic efficacy, resulting in significantly longer survival of mice, without inducing toxicity. These findings uncover the ICD potential of SCU and provide a promising strategy for HCC immunotherapy.</description><subject>Animals</subject><subject>Apigenin</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Drug delivery</subject><subject>Immunogenic Cell Death</subject><subject>Immunotherapy</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - metabolism</subject><subject>Mice</subject><subject>Nanoparticle</subject><subject>Tumor Microenvironment</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE9vGjEQxa0qVSG0H6GRj7kssT3G3j1VFWqbSCi9tGfX2LNgxNrE3kXi23cRJNecZqT33vz5EfKVszlnXD3s5mF32NrczQUTMOcCOJcfyJTXGiqQWt2QKQNdVwuuYUJuS9kxxpTg8IlMQAPjQsKU_Hu2MXnchyPmE00tLW7ocb-3OUQaoh8cFhq6bohpgzE46kaRerT9lrYp0z6PbYgbusWD7dNZHcYwdTa7EFNnP5OPrd0X_HKtM_L3548_y8dq9fvX0_L7qnKgFn0lWw21lNoqr3jDXa208tBwrRoNUniLqDxDwe3aSqhbqXVjxboVrIZGaw0zcn-Ze8jpZcDSmy6U8zk2YhqKEbWQqmELBaN1cbG6nErJ2JpDDp3NJ8OZOcM1O3OFa85wzQXumLu7rhjWHfq31CvN0fDtYsDx0WPAbIoLGB36kNH1xqfwzor_uQOOJA</recordid><startdate>20230725</startdate><enddate>20230725</enddate><creator>Li, Linlin</creator><creator>Zou, Yifang</creator><creator>Wang, Lingzhi</creator><creator>Yang, Leilei</creator><creator>Li, Yutong</creator><creator>Liao, Anqi</creator><creator>Chen, Zheng</creator><creator>Yu, Zhuo</creator><creator>Guo, Jianfeng</creator><creator>Han, Shulan</creator><general>Elsevier B.V</general><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>7X8</scope></search><sort><creationdate>20230725</creationdate><title>Nanodelivery of scutellarin induces immunogenic cell death for treating hepatocellular carcinoma</title><author>Li, Linlin ; Zou, Yifang ; Wang, Lingzhi ; Yang, Leilei ; Li, Yutong ; Liao, Anqi ; Chen, Zheng ; Yu, Zhuo ; Guo, Jianfeng ; Han, Shulan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-4f738447a6d6191c8676d3917697342daee6d0e21aba438f4779a2bf208397773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Apigenin</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Drug delivery</topic><topic>Immunogenic Cell Death</topic><topic>Immunotherapy</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - metabolism</topic><topic>Mice</topic><topic>Nanoparticle</topic><topic>Tumor Microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Linlin</creatorcontrib><creatorcontrib>Zou, Yifang</creatorcontrib><creatorcontrib>Wang, Lingzhi</creatorcontrib><creatorcontrib>Yang, Leilei</creatorcontrib><creatorcontrib>Li, Yutong</creatorcontrib><creatorcontrib>Liao, Anqi</creatorcontrib><creatorcontrib>Chen, Zheng</creatorcontrib><creatorcontrib>Yu, Zhuo</creatorcontrib><creatorcontrib>Guo, Jianfeng</creatorcontrib><creatorcontrib>Han, Shulan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Linlin</au><au>Zou, Yifang</au><au>Wang, Lingzhi</au><au>Yang, Leilei</au><au>Li, Yutong</au><au>Liao, Anqi</au><au>Chen, Zheng</au><au>Yu, Zhuo</au><au>Guo, Jianfeng</au><au>Han, Shulan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nanodelivery of scutellarin induces immunogenic cell death for treating hepatocellular carcinoma</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2023-07-25</date><risdate>2023</risdate><volume>642</volume><spage>123114</spage><epage>123114</epage><pages>123114-123114</pages><artnum>123114</artnum><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
Hepatocellular carcinoma (HCC) causes the immunosuppressive tumor microenvironment (TME) resistant to current immunotherapy. The immunogenic apoptosis (currently termed immunogenic cell death, ICD) of cancer cells may induce the adaptive immunity against tumors, thereby providing great potential for treating HCC. In this study, we have confirmed the potential of scutellarin (SCU, a flavonoid found in Erigeron breviscapus) for triggering ICD in HCC cells. To facilitate in vivo application of SCU for HCC immunotherapy, an aminoethyl anisamide-targeted polyethylene glycol-modified poly(lactide-co-glycolide) (PLGA-PEG-AEAA) was produced to facilitate SCU delivery in this study. The resultant nanoformulation (PLGA-PEG-AEAA.SCU) remarkably promoted blood circulation and tumor delivery in the orthotopic HCC mouse model. Consequently, PLGA-PEG-AEAA.SCU reversed the immune suppressive TME and achieved the immunotherapeutic efficacy, resulting in significantly longer survival of mice, without inducing toxicity. These findings uncover the ICD potential of SCU and provide a promising strategy for HCC immunotherapy.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>37301243</pmid><doi>10.1016/j.ijpharm.2023.123114</doi><tpages>1</tpages></addata></record> |
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| subjects | Animals Apigenin Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - metabolism Drug delivery Immunogenic Cell Death Immunotherapy Liver cancer Liver Neoplasms - drug therapy Liver Neoplasms - metabolism Mice Nanoparticle Tumor Microenvironment |
| title | Nanodelivery of scutellarin induces immunogenic cell death for treating hepatocellular carcinoma |
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