Loading…

Tumor localization of oncolytic adenovirus assisted by pH-degradable microgels with JQ1-mediated boosting replication and PD-L1 suppression for enhanced cancer therapy

Oncolytic therapy is a fast-developing cancer treatment field based on the promising clinical performance from the selective tumor cell killing and induction of systemic antitumor immunity. The virotherapy efficacy, however, is strongly hindered by the limited virus propagation and negative immune r...

Full description

Saved in:
Bibliographic Details
Published in:Biomaterials science 2020-05, Vol.8 (9), p.2472-248
Main Authors: Qiao, Haishi, Chen, Xingmei, Wang, Qiming, Zhang, Junmei, Huang, Dechun, Chen, Enping, Qian, Hongliang, Zhong, Yinan, Tang, Qi, Chen, Wei
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c399t-7a88700a8d1842c55a5095db113b34ecd5cb01e10a1f36589fadd82dd19f883
cites cdi_FETCH-LOGICAL-c399t-7a88700a8d1842c55a5095db113b34ecd5cb01e10a1f36589fadd82dd19f883
container_end_page 248
container_issue 9
container_start_page 2472
container_title Biomaterials science
container_volume 8
creator Qiao, Haishi
Chen, Xingmei
Wang, Qiming
Zhang, Junmei
Huang, Dechun
Chen, Enping
Qian, Hongliang
Zhong, Yinan
Tang, Qi
Chen, Wei
description Oncolytic therapy is a fast-developing cancer treatment field based on the promising clinical performance from the selective tumor cell killing and induction of systemic antitumor immunity. The virotherapy efficacy, however, is strongly hindered by the limited virus propagation and negative immune regulation in the tumor microenvironments. To enhance the antitumor activity, we developed injectable pH-degradable PVA microgels encapsulated with oncolytic adenovirus (OA) by microfluidics for localized OA delivery and cancer treatments. PVA microgels were tailored with an OA encapsulation efficiency of 68% and exhibited a pH-dependent OA release as the microgel degradation at mildly acidic conditions. PVA microgels mediated fast viral release and increased replication in HEK293T and A549 cells at a lower pH, and the replication efficiency could be further reinforced by co-loading with one BET bromodomain inhibitor JQ1, inducing significant cytotoxicity against A549 cells. An in vivo study revealed that OA release was highly located at the tumor tissue assisted by PVA microgels, and the OA infection was also enhanced with the addition of JQ1 treatment, meanwhile greatly inhibiting the PD-L1 expression to overcome the immune suppression. OA/JQ1 co-encapsulated injectable microgels exhibited a superior in vivo antitumor activity on the A549 lung tumor-bearing mice by the combination of inhibited proliferation, amplified oncolysis, and potential immune regulation. Illustration of pH-degradable microgels (MGs) for the simultaneous encapsulation of OA and JQ1 for an enhanced oncolytic viral treatment with JQ1-meidated boosting viral replication and PD-L1 suppression.
doi_str_mv 10.1039/d0bm00172d
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_32196028</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2381623472</sourcerecordid><originalsourceid>FETCH-LOGICAL-c399t-7a88700a8d1842c55a5095db113b34ecd5cb01e10a1f36589fadd82dd19f883</originalsourceid><addsrcrecordid>eNp9kktv1DAUha0K1Falm-6LjNhUSCl-5GEvoQMUNAgQ3Uc3tjPjyrGDnYCmf4i_idtppxKLenMt-_O5V-cYoRNKzinh8q0m3UAIbZjeQ4eMlE1RilI-2-05OUDHKV2TvJpGkpruowPOqKwJE4fo79U8hIhdUODsDUw2eBx6HLwKbjNZhUEbH37bOCcMKdk0GY27DR4vC21WETR0zuDBqhhWxiX8x05r_OUHLQajLdzBIaTJ-hWOZnRWbVuA1_j7olhSnOZxjCYr59M-T2L8GrzK79RtiXhamwjj5gV63oNL5vi-HqGfHz9cXVwWy2-fPl-8WxaKSzkVDQjREAJCU1EyVVVQEVnpjlLe8dIoXamOUEMJ0J7XlZA9aC2Y1lT2QvAjdLZVHWP4NZs0tYNNyjgH3oQ5tYwLWjNeNiyjr_9Dr8McfZ4tUzJHkA2uM_VmS2V_Uoqmb8doB4iblpL2Nr92Qd5_vctvkeGX95Jzl-3boQ9pZeDVFohJ7W4fP0A76j4zp08x_B8kg6z7</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2398499606</pqid></control><display><type>article</type><title>Tumor localization of oncolytic adenovirus assisted by pH-degradable microgels with JQ1-mediated boosting replication and PD-L1 suppression for enhanced cancer therapy</title><source>Royal Society of Chemistry</source><creator>Qiao, Haishi ; Chen, Xingmei ; Wang, Qiming ; Zhang, Junmei ; Huang, Dechun ; Chen, Enping ; Qian, Hongliang ; Zhong, Yinan ; Tang, Qi ; Chen, Wei</creator><creatorcontrib>Qiao, Haishi ; Chen, Xingmei ; Wang, Qiming ; Zhang, Junmei ; Huang, Dechun ; Chen, Enping ; Qian, Hongliang ; Zhong, Yinan ; Tang, Qi ; Chen, Wei</creatorcontrib><description>Oncolytic therapy is a fast-developing cancer treatment field based on the promising clinical performance from the selective tumor cell killing and induction of systemic antitumor immunity. The virotherapy efficacy, however, is strongly hindered by the limited virus propagation and negative immune regulation in the tumor microenvironments. To enhance the antitumor activity, we developed injectable pH-degradable PVA microgels encapsulated with oncolytic adenovirus (OA) by microfluidics for localized OA delivery and cancer treatments. PVA microgels were tailored with an OA encapsulation efficiency of 68% and exhibited a pH-dependent OA release as the microgel degradation at mildly acidic conditions. PVA microgels mediated fast viral release and increased replication in HEK293T and A549 cells at a lower pH, and the replication efficiency could be further reinforced by co-loading with one BET bromodomain inhibitor JQ1, inducing significant cytotoxicity against A549 cells. An in vivo study revealed that OA release was highly located at the tumor tissue assisted by PVA microgels, and the OA infection was also enhanced with the addition of JQ1 treatment, meanwhile greatly inhibiting the PD-L1 expression to overcome the immune suppression. OA/JQ1 co-encapsulated injectable microgels exhibited a superior in vivo antitumor activity on the A549 lung tumor-bearing mice by the combination of inhibited proliferation, amplified oncolysis, and potential immune regulation. Illustration of pH-degradable microgels (MGs) for the simultaneous encapsulation of OA and JQ1 for an enhanced oncolytic viral treatment with JQ1-meidated boosting viral replication and PD-L1 suppression.</description><identifier>ISSN: 2047-4830</identifier><identifier>EISSN: 2047-4849</identifier><identifier>DOI: 10.1039/d0bm00172d</identifier><identifier>PMID: 32196028</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>A549 Cells ; Adenoviridae ; Adenoviruses ; Animals ; Anticancer properties ; Azepines - administration &amp; dosage ; B7-H1 Antigen - antagonists &amp; inhibitors ; Biocompatibility ; Cancer ; Cancer therapies ; Degradation ; Encapsulation ; HEK293 Cells ; Humans ; Hydrogen-Ion Concentration ; In vivo methods and tests ; Localization ; Mice, Nude ; Microfluidics ; Microgels ; Microgels - administration &amp; dosage ; Neoplasms - therapy ; Oncolytic Virotherapy ; Proteins - antagonists &amp; inhibitors ; Replication ; Toxicity ; Triazoles - administration &amp; dosage ; Viruses</subject><ispartof>Biomaterials science, 2020-05, Vol.8 (9), p.2472-248</ispartof><rights>Copyright Royal Society of Chemistry 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-7a88700a8d1842c55a5095db113b34ecd5cb01e10a1f36589fadd82dd19f883</citedby><cites>FETCH-LOGICAL-c399t-7a88700a8d1842c55a5095db113b34ecd5cb01e10a1f36589fadd82dd19f883</cites><orcidid>0000-0003-4017-9722</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32196028$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qiao, Haishi</creatorcontrib><creatorcontrib>Chen, Xingmei</creatorcontrib><creatorcontrib>Wang, Qiming</creatorcontrib><creatorcontrib>Zhang, Junmei</creatorcontrib><creatorcontrib>Huang, Dechun</creatorcontrib><creatorcontrib>Chen, Enping</creatorcontrib><creatorcontrib>Qian, Hongliang</creatorcontrib><creatorcontrib>Zhong, Yinan</creatorcontrib><creatorcontrib>Tang, Qi</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><title>Tumor localization of oncolytic adenovirus assisted by pH-degradable microgels with JQ1-mediated boosting replication and PD-L1 suppression for enhanced cancer therapy</title><title>Biomaterials science</title><addtitle>Biomater Sci</addtitle><description>Oncolytic therapy is a fast-developing cancer treatment field based on the promising clinical performance from the selective tumor cell killing and induction of systemic antitumor immunity. The virotherapy efficacy, however, is strongly hindered by the limited virus propagation and negative immune regulation in the tumor microenvironments. To enhance the antitumor activity, we developed injectable pH-degradable PVA microgels encapsulated with oncolytic adenovirus (OA) by microfluidics for localized OA delivery and cancer treatments. PVA microgels were tailored with an OA encapsulation efficiency of 68% and exhibited a pH-dependent OA release as the microgel degradation at mildly acidic conditions. PVA microgels mediated fast viral release and increased replication in HEK293T and A549 cells at a lower pH, and the replication efficiency could be further reinforced by co-loading with one BET bromodomain inhibitor JQ1, inducing significant cytotoxicity against A549 cells. An in vivo study revealed that OA release was highly located at the tumor tissue assisted by PVA microgels, and the OA infection was also enhanced with the addition of JQ1 treatment, meanwhile greatly inhibiting the PD-L1 expression to overcome the immune suppression. OA/JQ1 co-encapsulated injectable microgels exhibited a superior in vivo antitumor activity on the A549 lung tumor-bearing mice by the combination of inhibited proliferation, amplified oncolysis, and potential immune regulation. Illustration of pH-degradable microgels (MGs) for the simultaneous encapsulation of OA and JQ1 for an enhanced oncolytic viral treatment with JQ1-meidated boosting viral replication and PD-L1 suppression.</description><subject>A549 Cells</subject><subject>Adenoviridae</subject><subject>Adenoviruses</subject><subject>Animals</subject><subject>Anticancer properties</subject><subject>Azepines - administration &amp; dosage</subject><subject>B7-H1 Antigen - antagonists &amp; inhibitors</subject><subject>Biocompatibility</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Degradation</subject><subject>Encapsulation</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>In vivo methods and tests</subject><subject>Localization</subject><subject>Mice, Nude</subject><subject>Microfluidics</subject><subject>Microgels</subject><subject>Microgels - administration &amp; dosage</subject><subject>Neoplasms - therapy</subject><subject>Oncolytic Virotherapy</subject><subject>Proteins - antagonists &amp; inhibitors</subject><subject>Replication</subject><subject>Toxicity</subject><subject>Triazoles - administration &amp; dosage</subject><subject>Viruses</subject><issn>2047-4830</issn><issn>2047-4849</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kktv1DAUha0K1Falm-6LjNhUSCl-5GEvoQMUNAgQ3Uc3tjPjyrGDnYCmf4i_idtppxKLenMt-_O5V-cYoRNKzinh8q0m3UAIbZjeQ4eMlE1RilI-2-05OUDHKV2TvJpGkpruowPOqKwJE4fo79U8hIhdUODsDUw2eBx6HLwKbjNZhUEbH37bOCcMKdk0GY27DR4vC21WETR0zuDBqhhWxiX8x05r_OUHLQajLdzBIaTJ-hWOZnRWbVuA1_j7olhSnOZxjCYr59M-T2L8GrzK79RtiXhamwjj5gV63oNL5vi-HqGfHz9cXVwWy2-fPl-8WxaKSzkVDQjREAJCU1EyVVVQEVnpjlLe8dIoXamOUEMJ0J7XlZA9aC2Y1lT2QvAjdLZVHWP4NZs0tYNNyjgH3oQ5tYwLWjNeNiyjr_9Dr8McfZ4tUzJHkA2uM_VmS2V_Uoqmb8doB4iblpL2Nr92Qd5_vctvkeGX95Jzl-3boQ9pZeDVFohJ7W4fP0A76j4zp08x_B8kg6z7</recordid><startdate>20200506</startdate><enddate>20200506</enddate><creator>Qiao, Haishi</creator><creator>Chen, Xingmei</creator><creator>Wang, Qiming</creator><creator>Zhang, Junmei</creator><creator>Huang, Dechun</creator><creator>Chen, Enping</creator><creator>Qian, Hongliang</creator><creator>Zhong, Yinan</creator><creator>Tang, Qi</creator><creator>Chen, Wei</creator><general>Royal Society of Chemistry</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>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4017-9722</orcidid></search><sort><creationdate>20200506</creationdate><title>Tumor localization of oncolytic adenovirus assisted by pH-degradable microgels with JQ1-mediated boosting replication and PD-L1 suppression for enhanced cancer therapy</title><author>Qiao, Haishi ; Chen, Xingmei ; Wang, Qiming ; Zhang, Junmei ; Huang, Dechun ; Chen, Enping ; Qian, Hongliang ; Zhong, Yinan ; Tang, Qi ; Chen, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-7a88700a8d1842c55a5095db113b34ecd5cb01e10a1f36589fadd82dd19f883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>A549 Cells</topic><topic>Adenoviridae</topic><topic>Adenoviruses</topic><topic>Animals</topic><topic>Anticancer properties</topic><topic>Azepines - administration &amp; dosage</topic><topic>B7-H1 Antigen - antagonists &amp; inhibitors</topic><topic>Biocompatibility</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Degradation</topic><topic>Encapsulation</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>In vivo methods and tests</topic><topic>Localization</topic><topic>Mice, Nude</topic><topic>Microfluidics</topic><topic>Microgels</topic><topic>Microgels - administration &amp; dosage</topic><topic>Neoplasms - therapy</topic><topic>Oncolytic Virotherapy</topic><topic>Proteins - antagonists &amp; inhibitors</topic><topic>Replication</topic><topic>Toxicity</topic><topic>Triazoles - administration &amp; dosage</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qiao, Haishi</creatorcontrib><creatorcontrib>Chen, Xingmei</creatorcontrib><creatorcontrib>Wang, Qiming</creatorcontrib><creatorcontrib>Zhang, Junmei</creatorcontrib><creatorcontrib>Huang, Dechun</creatorcontrib><creatorcontrib>Chen, Enping</creatorcontrib><creatorcontrib>Qian, Hongliang</creatorcontrib><creatorcontrib>Zhong, Yinan</creatorcontrib><creatorcontrib>Tang, Qi</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><jtitle>Biomaterials science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qiao, Haishi</au><au>Chen, Xingmei</au><au>Wang, Qiming</au><au>Zhang, Junmei</au><au>Huang, Dechun</au><au>Chen, Enping</au><au>Qian, Hongliang</au><au>Zhong, Yinan</au><au>Tang, Qi</au><au>Chen, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor localization of oncolytic adenovirus assisted by pH-degradable microgels with JQ1-mediated boosting replication and PD-L1 suppression for enhanced cancer therapy</atitle><jtitle>Biomaterials science</jtitle><addtitle>Biomater Sci</addtitle><date>2020-05-06</date><risdate>2020</risdate><volume>8</volume><issue>9</issue><spage>2472</spage><epage>248</epage><pages>2472-248</pages><issn>2047-4830</issn><eissn>2047-4849</eissn><abstract>Oncolytic therapy is a fast-developing cancer treatment field based on the promising clinical performance from the selective tumor cell killing and induction of systemic antitumor immunity. The virotherapy efficacy, however, is strongly hindered by the limited virus propagation and negative immune regulation in the tumor microenvironments. To enhance the antitumor activity, we developed injectable pH-degradable PVA microgels encapsulated with oncolytic adenovirus (OA) by microfluidics for localized OA delivery and cancer treatments. PVA microgels were tailored with an OA encapsulation efficiency of 68% and exhibited a pH-dependent OA release as the microgel degradation at mildly acidic conditions. PVA microgels mediated fast viral release and increased replication in HEK293T and A549 cells at a lower pH, and the replication efficiency could be further reinforced by co-loading with one BET bromodomain inhibitor JQ1, inducing significant cytotoxicity against A549 cells. An in vivo study revealed that OA release was highly located at the tumor tissue assisted by PVA microgels, and the OA infection was also enhanced with the addition of JQ1 treatment, meanwhile greatly inhibiting the PD-L1 expression to overcome the immune suppression. OA/JQ1 co-encapsulated injectable microgels exhibited a superior in vivo antitumor activity on the A549 lung tumor-bearing mice by the combination of inhibited proliferation, amplified oncolysis, and potential immune regulation. Illustration of pH-degradable microgels (MGs) for the simultaneous encapsulation of OA and JQ1 for an enhanced oncolytic viral treatment with JQ1-meidated boosting viral replication and PD-L1 suppression.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>32196028</pmid><doi>10.1039/d0bm00172d</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-4017-9722</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2047-4830
ispartof Biomaterials science, 2020-05, Vol.8 (9), p.2472-248
issn 2047-4830
2047-4849
language eng
recordid cdi_pubmed_primary_32196028
source Royal Society of Chemistry
subjects A549 Cells
Adenoviridae
Adenoviruses
Animals
Anticancer properties
Azepines - administration & dosage
B7-H1 Antigen - antagonists & inhibitors
Biocompatibility
Cancer
Cancer therapies
Degradation
Encapsulation
HEK293 Cells
Humans
Hydrogen-Ion Concentration
In vivo methods and tests
Localization
Mice, Nude
Microfluidics
Microgels
Microgels - administration & dosage
Neoplasms - therapy
Oncolytic Virotherapy
Proteins - antagonists & inhibitors
Replication
Toxicity
Triazoles - administration & dosage
Viruses
title Tumor localization of oncolytic adenovirus assisted by pH-degradable microgels with JQ1-mediated boosting replication and PD-L1 suppression for enhanced cancer therapy
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T19%3A55%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tumor%20localization%20of%20oncolytic%20adenovirus%20assisted%20by%20pH-degradable%20microgels%20with%20JQ1-mediated%20boosting%20replication%20and%20PD-L1%20suppression%20for%20enhanced%20cancer%20therapy&rft.jtitle=Biomaterials%20science&rft.au=Qiao,%20Haishi&rft.date=2020-05-06&rft.volume=8&rft.issue=9&rft.spage=2472&rft.epage=248&rft.pages=2472-248&rft.issn=2047-4830&rft.eissn=2047-4849&rft_id=info:doi/10.1039/d0bm00172d&rft_dat=%3Cproquest_pubme%3E2381623472%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c399t-7a88700a8d1842c55a5095db113b34ecd5cb01e10a1f36589fadd82dd19f883%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2398499606&rft_id=info:pmid/32196028&rfr_iscdi=true