{"id":176,"date":"2025-05-27T19:04:11","date_gmt":"2025-05-27T19:04:11","guid":{"rendered":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/?p=176"},"modified":"2025-05-27T19:04:11","modified_gmt":"2025-05-27T19:04:11","slug":"multimodal-imaging-demonstrates-enhanced-tumor-exposure-of-pegylated-fud-peptide-in-breast-cancer","status":"publish","type":"post","link":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/2025\/05\/27\/multimodal-imaging-demonstrates-enhanced-tumor-exposure-of-pegylated-fud-peptide-in-breast-cancer\/","title":{"rendered":"Multimodal imaging demonstrates enhanced tumor exposure of PEGylated FUD peptide in breast cancer"},"content":{"rendered":"
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October 1, 2022<\/div>\r\nCite this<\/a><\/div>\r\n
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Abstract<\/h2>\r\n
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https:\/\/doi.org\/10.1016\/j.jconrel.2022.08.028<\/figcaption><\/figure>\r\n\r\nIn breast cancer, the extracellular matrix (ECM) undergoes remodeling and changes the\u00a0tumor microenvironment<\/a>\u00a0to support tumor progression and metastasis.\u00a0Fibronectin<\/a>\u00a0(FN) assembly is an important step in the regulation of the tumor microenvironment since the FN matrix precedes the deposition of various other\u00a0ECM proteins<\/a>, controls immune cell\u00a0infiltration<\/a>, and serves as a reservoir for cytokines and growth factors. Therefore, FN is an attractive target for breast cancer therapy and imaging. Functional Upstream Domain (FUD) is a 6-kDa peptide targeting the N-terminal 70-kDa domain of FN, which is critical for fibrillogenesis. FUD has previously been shown to function as an anti-fibrotic peptide both\u00a0in vitro<\/em>\u00a0and\u00a0in vivo<\/em>. In this work, we conjugated the FUD peptide with 20-kDa of\u00a0PEG<\/a>\u00a0(PEG-FUD) and demonstrated its improved tumor exposure compared to non-PEGylated FUD in a murine breast cancer model\u00a0via<\/em>\u00a0multiple imaging modalities. Importantly, PEG-FUD peptide retained a nanomolar binding affinity for FN and maintained\u00a0in vitro<\/em>\u00a0plasma stability for up to 48\u00a0h. Cy5-labeled PEG-FUD bound to exogenous or endogenous FN assembled by fibroblasts. The\u00a0in vivo<\/em>\u00a0fluorescence imaging with Cy5-labeled FUD and FUD conjugates demonstrated that\u00a0PEGylation<\/a>\u00a0of the FUD peptide enhanced blood exposure after subcutaneous (SC) injection and significantly increased accumulation of FUD peptide in 4T1 mammary tumors.\u00a0Intravital microscopy<\/a>\u00a0confirmed that Cy5-labeled PEG-FUD deposited mostly in the extravascular region of the tumor microenvironment after SC administration. Lastly, positron emission tomography\/computed\u00a0tomography<\/a>\u00a0imaging showed that\u00a064<\/sup>Cu-labeled PEG-FUD preferentially accumulated in the 4T1 tumors with improved tumor uptake compared to\u00a064<\/sup>Cu-labeled FUD (48\u00a0h: 1.35\u00a0\u00b1\u00a00.05\u00a0vs.<\/em>\u00a00.59\u00a0\u00b1\u00a00.03 %IA\/g,\u00a0P<\/em>\u00a0<\u00a00.001) when injected intravenously (IV). The results indicate that PEG-FUD targets 4T1 breast cancer with enhanced tumor retention compared to non-PEGylated FUD, and\u00a0biodistribution<\/a>\u00a0profiles of PEG-FUD after SC and IV injection may guide the optimization of PEG-FUD as a therapeutic and\/or imaging agent for use\u00a0in vivo<\/em>.\r\n\r\n<\/div>\r\n<\/div>\r\n<\/section><\/section><\/div>","protected":false},"excerpt":{"rendered":"October 1, 2022 Cite this Abstract In breast cancer, the extracellular matrix (ECM) undergoes remodeling and changes the\u00a0tumor microenvironment\u00a0to support tumor progression and metastasis.\u00a0Fibronectin\u00a0(FN) assembly is an important step in the regulation of the tumor …","protected":false},"author":7,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-176","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"acf":[],"_links":{"self":[{"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/posts\/176","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/comments?post=176"}],"version-history":[{"count":1,"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/posts\/176\/revisions"}],"predecessor-version":[{"id":177,"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/posts\/176\/revisions\/177"}],"wp:attachment":[{"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/media?parent=176"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/categories?post=176"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/kwon-research-group\/wp-json\/wp\/v2\/tags?post=176"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}