ONP-302 Nanoparticles Inhibit Tumor Growth By Altering Tumor-Associated Macrophages And Cancer-Associated Fibroblasts

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Therapeutic treatment with ONP-302 in vivo resulted in a marked delay in tumor growth in three different syngeneic tumor models in immunocompetent mice. ONP- 302 efficacy pe …"><meta name="keywords" content="pmid:35399717, PMC8990435, doi:10.7150/jca.69338, Laxminarasimha Donthireddy, Prashanthi Vonteddu, Dmitry I Gabrilovich, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="ONP-302 Nanoparticles Inhibit Tumor Growth By Altering Tumor-Associated Macrophages And Cancer-Associated Fibroblasts - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/35399717/"><meta property="og:description" content="In this study, we evaluated the ability of negatively charged bio-degradable nanoparticles, ONP- 302, to inhibit tumor growth. Therapeutic treatment with ONP-302 in vivo resulted in a marked delay in tumor growth in three different syngeneic tumor models in immunocompetent mice. ONP- 302 efficacy pe …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="ONP-302 Nanoparticles Inhibit Tumor Growth By Altering Tumor-Associated Macrophages And Cancer-Associated Fibroblasts - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/35399717/"><meta name="twitter:description" content="In this study, we evaluated the ability of negatively charged bio-degradable nanoparticles, ONP- 302, to inhibit tumor growth. Therapeutic treatment with ONP-302 in vivo resulted in a marked delay in tumor growth in three different syngeneic tumor models in immunocompetent mice. 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new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="CxJ8vXvZo9absg5q1lAo44xffMXrh90jtTQC3fRUWS8mFdtvy9dc5mq00urMwHnS"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="CxJ8vXvZo9absg5q1lAo44xffMXrh90jtTQC3fRUWS8mFdtvy9dc5mq00urMwHnS"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="CxJ8vXvZo9absg5q1lAo44xffMXrh90jtTQC3fRUWS8mFdtvy9dc5mq00urMwHnS"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="CxJ8vXvZo9absg5q1lAo44xffMXrh90jtTQC3fRUWS8mFdtvy9dc5mq00urMwHnS"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> 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class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Donthireddy+L&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Laxminarasimha Donthireddy">Laxminarasimha Donthireddy</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Vonteddu+P&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Prashanthi Vonteddu">Prashanthi Vonteddu</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Murthy+T&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Tushar Murthy">Tushar Murthy</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Research & Development, Cour Pharmaceuticals Development Company, Northbrook, IL, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Kwak+T&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Taekyoung Kwak">Taekyoung Kwak</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Eraslan+RN&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Rukiye-Nazan Eraslan">Rukiye-Nazan Eraslan</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Invivotek, Genesis Drug Discovery and Development (GD3), Hamilton, NJ, USA." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Podojil+JR&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" 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Development Company, Northbrook, IL, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Boyne+MT+2nd&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Michael T Boyne 2nd">Michael T Boyne 2nd</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Research & Development, Cour Pharmaceuticals Development Company, Northbrook, IL, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Microbiology and Immunology, Northwestern University, Chicago, IL, USA." href="#full-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" 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class="author-sup-separator"> </span><a class="affiliation-link" title="Current affiliation: H. 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</div> <span class="citation-doi"> doi: 10.7150/jca.69338. </span> <span class="secondary-date"> eCollection 2022. </span> </div> <div class="expanded-authors" id="short-view-expanded-authors"> <div class="authors"> <h3 class="title"> Authors </h3> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Donthireddy+L&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Laxminarasimha Donthireddy">Laxminarasimha Donthireddy</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Vonteddu+P&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Prashanthi Vonteddu">Prashanthi Vonteddu</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Murthy+T&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Tushar Murthy">Tushar Murthy</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Research & Development, Cour Pharmaceuticals Development Company, Northbrook, IL, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Kwak+T&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Taekyoung Kwak">Taekyoung Kwak</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Eraslan+RN&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Rukiye-Nazan Eraslan">Rukiye-Nazan Eraslan</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Invivotek, Genesis Drug Discovery and Development (GD3), Hamilton, NJ, USA." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Podojil+JR&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Joseph R Podojil">Joseph R Podojil</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Research & Development, Cour Pharmaceuticals Development Company, Northbrook, IL, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Microbiology and Immunology, Northwestern University, Chicago, IL, USA." href="#short-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Elhofy+A&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Adam Elhofy">Adam Elhofy</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Research & Development, Cour Pharmaceuticals Development Company, Northbrook, IL, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Boyne+MT+2nd&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Michael T Boyne 2nd">Michael T Boyne 2nd</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Research & Development, Cour Pharmaceuticals Development Company, Northbrook, IL, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Microbiology and Immunology, Northwestern University, Chicago, IL, USA." href="#short-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Puisis+JJ&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="John J Puisis">John J Puisis</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Research & Development, Cour Pharmaceuticals Development Company, Northbrook, IL, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Veglia+F&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Filippo Veglia">Filippo Veglia</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Current affiliation: H. Lee Moffitt Cancer Center, Tampa, FL." href="#short-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Singh+SS&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Surya S Singh">Surya S Singh</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Biochemistry, Osmania University, Hyderabad, India." href="#short-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Dotiwala+F&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Farokh Dotiwala">Farokh Dotiwala</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Montaner+LJ&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Luis J Montaner">Luis J Montaner</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gabrilovich+DI&cauthor_id=35399717" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Dmitry I Gabrilovich">Dmitry I Gabrilovich</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, 19104, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Current affiliation: ICC, Early Oncology R&D, AstraZeneca, Gaithersburg, 20878, USA." href="#short-view-affiliation-8" ref="linksrc=author_aff"> 8 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, 19104, USA.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA.</li> <li data-affiliation-id="short-view-affiliation-3" id="short-view-affiliation-3" ><sup class="key">3</sup> Research & Development, Cour Pharmaceuticals Development Company, Northbrook, IL, USA.</li> <li data-affiliation-id="short-view-affiliation-4" id="short-view-affiliation-4" ><sup class="key">4</sup> Invivotek, Genesis Drug Discovery and Development (GD3), Hamilton, NJ, USA.</li> <li data-affiliation-id="short-view-affiliation-5" id="short-view-affiliation-5" ><sup class="key">5</sup> Department of Microbiology and Immunology, Northwestern University, Chicago, IL, USA.</li> <li data-affiliation-id="short-view-affiliation-6" id="short-view-affiliation-6" ><sup class="key">6</sup> Current affiliation: H. Lee Moffitt Cancer Center, Tampa, FL.</li> <li data-affiliation-id="short-view-affiliation-7" id="short-view-affiliation-7" ><sup class="key">7</sup> Department of Biochemistry, Osmania University, Hyderabad, India.</li> <li data-affiliation-id="short-view-affiliation-8" id="short-view-affiliation-8" ><sup class="key">8</sup> Current affiliation: ICC, Early Oncology R&D, AstraZeneca, Gaithersburg, 20878, USA.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">35399717</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC8990435&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8990435/" data-ga-category="full_text" data-ga-action="PMCID" > PMC8990435 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.7150/jca.69338&id_type=DOI" href="https://doi.org/10.7150/jca.69338" data-ga-category="full_text" data-ga-action="DOI" > 10.7150/jca.69338 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/35399717/citations/" data-citation-style="nlm" data-pubmed-format-link="/35399717/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> In this study, we evaluated the ability of negatively charged bio-degradable nanoparticles, ONP- 302, to inhibit tumor growth. Therapeutic treatment with ONP-302 in vivo resulted in a marked delay in tumor growth in three different syngeneic tumor models in immunocompetent mice. ONP- 302 efficacy persisted with depletion of CD8+ T cells in immunocompetent mice and also was effective in immune deficient mice. Examination of ONP-302 effects on components of the tumor microenvironment (TME) were explored. ONP-302 treatment caused a gene expression shift in TAMs toward the pro-inflammatory M1 type and substantially inhibited the expression of genes associated with the pro-tumorigenic function of CAFs. ONP-302 also induced apoptosis in CAFs in the TME. Together, these data support further development of ONP-302 as a novel first-in- class anti-cancer therapeutic that can be used as a single-agent as well as in combination therapies for the treatment of solid tumors due to its ability to modulate the TME. </p> </div> <p> <strong class="sub-title"> Keywords: </strong> Cancer Associated Fibroblasts (CAFs); M-MDSC.; MDSC; Nanoparticles; PMN-MDSC; Tumor Associated Macrophages (TAMs); Tumor Microenvironment. </p> </div> <p class="copyright" id="copyright"> © The author(s). </p> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="conflict-of-interest" id="conflict-of-interest"> <h2 class="title"> Conflict of interest statement </h2> <div class="statement"> <p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">Competing Interests: TM, JRP, AE, MTB, JJP are employees of Cour Pharmaceuticals, RE-is employee of invivotek, DIG - is employee of AstraZeneca.</p> </div> </div> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/f55981535ac1/jcav13p1933g001.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="775" data-image-height="433" data-image-alt="Figure 1" data-pmc-id="PMC8990435" data-figure-id="F1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/4c6a01afe8fc/jcav13p1933g001.gif" alt="Figure 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="775"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="433"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><b> Effect of ONP-302 on tumor… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><b> Effect of ONP-302 on tumor growth in different tumor models. </b> C57BL/6 mice (n=10)…</div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 1 </strong> <div class="figure-caption-contents"><b> Effect of ONP-302 on tumor growth in different tumor models.</b> C57BL/6 mice (n=10) were injected with 1 x 10<sup>6</sup> MC-38 cells and 0.5 x 10<sup>6</sup> LLC and B16F10 cells. Treatments with ONP-302 intravenously 50mg/kg biw started at ~50 mm<sup>2</sup> tumor size after tumor injection. Anti-PD1 antibody (100μg per mouse, intraperitonially) administered biw. Tumor growth of <b>(A)</b> B16 <b>(B)</b> LLC and <b>(C)</b> MC-38 tumor bearing mice administered the indicated treatments. <b>D</b>. Tumor growth in MC-38 tumor-bearing C57BL/6 mice administered anti-CD8 for T-cell depletion and treated with ONP-302 or Saline (Control). <b>E</b>. Tumor growth in LLC tumor-bearing NSG mice treated with ONP-302 or Saline (Control). The tumor size was measured by vernier calipers before and after the treatment day of every ONP-302 injection. Statistical differences in tumor growth were evaluated using Two-Way Anova test (***p<0.001).</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/6c7ae9e1ee63/jcav13p1933g002.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="753" data-image-height="435" data-image-alt="Figure 2" data-pmc-id="PMC8990435" data-figure-id="F2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/f3effebf4aaa/jcav13p1933g002.gif" alt="Figure 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="753"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="435"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><b> Effect of ONP-302 on immune-cell… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><b> Effect of ONP-302 on immune-cell composition in the TME </b> . LLC ( <b> A… </b></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2 </strong> <div class="figure-caption-contents"><b> Effect of ONP-302 on immune-cell composition in the TME</b>. LLC (<b>A</b>) tumor bearing C57BL/6 mice and MC-38 (<b>B</b>) tumor-bearing C57BL/6 mice were treated with vehicle or ONP-302 50mg/kg intravenously twice per week for 2 weeks. Single-cell suspensions were prepared from tumor and analyzed by flowcytometry. Percentages of T-cells (CD3+CD4+ or CD3+CD8+), NK cells (CD3- NK1.1+), TAM (CD11b+F4/80+), M-MDSC (CD11b+ Ly6Chi Ly6G-), and PMN-MDSC (CD11b+ Ly6C- Ly6G+) were measured.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/b2084acb44d3/jcav13p1933g003.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="760" data-image-height="502" data-image-alt="Figure 3" data-pmc-id="PMC8990435" data-figure-id="F3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/ded9bfb8d148/jcav13p1933g003.gif" alt="Figure 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="760"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="502"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><b> Effect of ONP-302 on gene… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><b> Effect of ONP-302 on gene expression in tumor-associated macrophages (TAMs) and fibroblasts. </b> LLC…</div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 3 </strong> <div class="figure-caption-contents"><b>Effect of ONP-302 on gene expression in tumor-associated macrophages (TAMs) and fibroblasts.</b> LLC tumor bearing C57BL/6 mice were treated with vehicle or ONP-302 50mg/kg intravenously twice per week for 2 weeks. Single-cell suspensions were prepared from tumor. TAMs and fibroblasts were sorted by fluorescence activated cell-sorting. <b>A</b>. Effect of ONP-302 treatment on the percentage of TAM (CD11b+F4/80+) in the tumor. <b>B</b>. Effect of ONP-302 on the expression of indicated genes in TAMs assayed by q-PCR. Relative gene expression was normalized to GAPDH. <b>C.</b> Effect of ONP- 302 treatment on the percentage of CAFs (CD45-CD140a+CD326-) in the tumor. Effect of ONP-302 on the expression of indicated genes in CAFs assayed by q-PCR. Relative gene expression was normalized to GAPDH and calculated by the comparative C(T) method .</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/eda667ad475d/jcav13p1933g004.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="772" data-image-height="475" data-image-alt="Figure 4" data-pmc-id="PMC8990435" data-figure-id="F4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/afeb43c75a78/jcav13p1933g004.gif" alt="Figure 4" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="772"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="475"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><b> Evaluation of particle-positive cells in… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><b> Evaluation of particle-positive cells in the tumor and spleen </b> . LLC tumor bearing…</div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 4 </strong> <div class="figure-caption-contents"><b> Evaluation of particle-positive cells in the tumor and spleen</b>. LLC tumor bearing C57BL/6 mice were intravenously treated injected with fluorescently labelled (Alexa-Fluor 647) ONP-302 50mg/kg. 2 hours after injection, single-cell suspensions were prepared from tumor and spleen and ONP-302-positive cells were analyzed by flow cytometry. <b>A</b>. Flow cytometry gating scheme for identifying ONP-302-positive TAMs (CD11b+F4/80+), M-MDSC (CD11b+ Ly6Chi Ly6G-), and PMN-MDSC (CD11b+ Ly6C- Ly6G+), and CAFs (CD45-CD140a+CD326-). <b>B</b>. Frequency of Alexa-Fluor 647-positive TAMs (CD11b+F4/80+), M-MDSC (CD11b+ Ly6Chi Ly6G-), and PMN-MDSC (CD11b+ Ly6C- Ly6G+), and CAFs (CD45- CD140a+CD326-) in LLC tumors. <b>C</b>. Frequency of Alexa-Fluor 647-positive macrophages (CD11b+F4/80+), monocytes (M-MDSC) (CD11b+ Ly6Chi Ly6G-), and neutrophils (PMN-MDSC) (CD11b+ Ly6C- Ly6G+) in spleens of LLC tumor-bearing mice.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="4" data-label-slug="figure-5"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/947917bce2a7/jcav13p1933g005.jpg" itemprop="contentUrl" aria-describedby="figure-caption-4" role="button" data-image-width="779" data-image-height="345" data-image-alt="Figure 5" data-pmc-id="PMC8990435" data-figure-id="F5"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-4" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/11a2bdee0803/jcav13p1933g005.gif" alt="Figure 5" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="779"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="345"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 5 </p> </strong> <div class="figure-caption-contents"><b> Induction of Apoptosis by ONP-302.… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 5 </p> </strong> <div class="figure-caption-contents"><b> Induction of Apoptosis by ONP-302. </b> LLC tumor bearing C57BL/6 mice were intravenously injected…</div> </div> <figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 5 </strong> <div class="figure-caption-contents"><b> Induction of Apoptosis by ONP-302.</b> LLC tumor bearing C57BL/6 mice were intravenously injected with fluorescently labeled (Alexa-Fluor 647) ONP-302 50mg/kg. for 2 weeks. 2 hours after last treatment, mice were sacrificed, and single-cell suspensions were prepared from the tumor and spleen. Induction of Apoptosis by ONP-302 was analyzed by flow cytometry. <b>A</b>. Flow cytometry gating scheme for identifying apoptotic TAMs (CD11b+F4/80+), M-MDSC (CD11b+ Ly6Chi Ly6G-), and PMN-MDSC (CD11b+ Ly6C- Ly6G+) and CAFs (CD45-CD140a+CD326-) using the indicated cell-surface markers. <b>B</b>. Flow cytometry analysis of indicated apoptotic cells in tumor.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="5" data-label-slug="figure-6"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/80f32e3ca625/jcav13p1933g006.jpg" itemprop="contentUrl" aria-describedby="figure-caption-5" role="button" data-image-width="761" data-image-height="321" data-image-alt="Figure 6" data-pmc-id="PMC8990435" data-figure-id="F6"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-5" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/7aac29f2d23a/jcav13p1933g006.gif" alt="Figure 6" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="761"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="321"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 6 </p> </strong> <div class="figure-caption-contents"><p> Apoptosis of cancer associated fibroblasts… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 6 </p> </strong> <div class="figure-caption-contents"><p> Apoptosis of cancer associated fibroblasts (CSF) in LLC mice treated with CNP-302. LLC… </p></div> </div> <figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 6 </strong> <div class="figure-caption-contents">Apoptosis of cancer associated fibroblasts (CSF) in LLC mice treated with CNP-302. LLC tumor-bearing mice were treated with ONP-302 (50mg/kg) intravenously twice per week for 2 weeks and tumor tissues were prepared for the staining. <b>A.</b> Typical example of tumor tissue staining with αSMA. Scale = 50 μm. <b>B</b>. Typical example of Masson's trichrome staining = 50 μm.</div> </figcaption> </figure> <figure class="figure-item tail" itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="6" data-label-slug="figure-7"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/f2cab692f7f0/jcav13p1933g007.jpg" itemprop="contentUrl" aria-describedby="figure-caption-6" role="button" data-image-width="740" data-image-height="402" data-image-alt="Figure 7" data-pmc-id="PMC8990435" data-figure-id="F7"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-6" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/8990435/0034295965a4/jcav13p1933g007.gif" alt="Figure 7" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="740"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="402"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 7 </p> </strong> <div class="figure-caption-contents"><p> Schematic Illustration of the ONP-302… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 7 </p> </strong> <div class="figure-caption-contents"><p> Schematic Illustration of the ONP-302 Mechanism. Details are provided in the text. </p></div> </div> <figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 7 </strong> <div class="figure-caption-contents">Schematic Illustration of the ONP-302 Mechanism. 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ONP-302 Nanoparticles Inhibit Tumor Growth By Altering Tumor-Associated Macrophages And Cancer-Associated Fibroblasts - PubMed