Fibroblast Activation Protein-Targeted Photodynamic Therapy of Cancer-Associated Fibroblasts in Murine Models for Pancreatic Ductal Adenocarcinoma

Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5 year survival of 9%. One important limiting factor for treatment efficacy is the dense tumor-supporting stroma. The cancer-associated fibroblasts in this stroma deposit excessive amounts of extracellular matrix components and anti...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Molecular pharmaceutics 2023-08, Vol.20 (8), p.4319-4330
Hauptverfasser: Dorst, Daphne N., Smeets, Esther M. M., Klein, Christian, Frielink, Cathelijne, Geijs, Daan, Trajkovic-Arsic, Marija, Cheung, Phyllis F. Y., Stommel, Martijn W. J., Gotthardt, Martin, Siveke, Jens T., Aarntzen, Erik H. J. G., van Lith, Sanne A. M.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 4330
container_issue 8
container_start_page 4319
container_title Molecular pharmaceutics
container_volume 20
creator Dorst, Daphne N.
Smeets, Esther M. M.
Klein, Christian
Frielink, Cathelijne
Geijs, Daan
Trajkovic-Arsic, Marija
Cheung, Phyllis F. Y.
Stommel, Martijn W. J.
Gotthardt, Martin
Siveke, Jens T.
Aarntzen, Erik H. J. G.
van Lith, Sanne A. M.
description Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5 year survival of 9%. One important limiting factor for treatment efficacy is the dense tumor-supporting stroma. The cancer-associated fibroblasts in this stroma deposit excessive amounts of extracellular matrix components and anti-inflammatory mediators, which hampers the efficacy of chemo- and immunotherapies. Systemic depletion of all activated fibroblasts is, however, not feasible nor desirable and therefore a local approach should be pursued. Here, we provide a proof-of-principle of using fibroblast activation protein (FAP)-targeted photodynamic therapy (tPDT) to treat PDAC. FAP-targeting antibody 28H1 and irrelevant control antibody DP47GS were conjugated to the photosensitizer IRDye700DX (700DX) and the chelator diethylenetriaminepentaacetic acid. In vitro binding and cytotoxicity were evaluated using the fibroblast cell-line NIH-3T3 stably transfected with FAP. Biodistribution of 111In-labeled antibody-700DX constructs was determined in mice carrying syngeneic tumors of the murine PDAC cell line PDAC299, and in a genetically engineered PDAC mouse model (CKP). Then, tPDT was performed by exposing the subcutaneous or the spontaneous PDAC tumors to 690 nm light. Induction of apoptosis after treatment was assessed using automated analyses of immunohistochemistry for cleaved caspase-3. 28H1-700DX effectively bound to 3T3-FAP cells and induced cytotoxicity upon exposure to 690 nm light, whereas no binding or cytotoxic effects were observed for DP47GS-700DX. Although both 28H1-700DX and DP47GS-700DX accumulated in subcutaneous PDAC299 tumors, autoradiography demonstrated that only 28H1-700DX reached the tumor core. On the contrary, control antibody DP47GS-700DX was only present at the tumor rim. In CKP mice, both antibodies accumulated in the tumor, but tumor-to-blood ratios of 28H1-700DX were higher than that of the control. Notably, in vivo FAP-tPDT caused upregulation of cleaved caspase-3 staining in both subcutaneous and in spontaneous tumors. In conclusion, we have shown that tPDT is a feasible approach for local depletion of FAP-expressing stromal cells in murine models for PDAC.
doi_str_mv 10.1021/acs.molpharmaceut.3c00453
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10410663</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2841401078</sourcerecordid><originalsourceid>FETCH-LOGICAL-a470t-980bcdfb38fc06d232c58ba3a2b3931aba62362ad056a849e038e0490bc34ef73</originalsourceid><addsrcrecordid>eNqNkctuEzEUhq0KRC_wCsjs2EzwbSaeFYpCW5BakUVYW2c8ZxpXM3awPZXyGjxxJ0pI6Y6VLfn_v3Pkj5BPnM04E_wL2DQbQr_dQBzA4phn0jKmSnlGLnipZKFlLd6c7lqdk8uUHhkTqhTyHTmXc6VLrasL8ufGNTE0PaRMFza7J8gueLqKIaPzxRriA2Zs6WoTcmh3HgZn6XqDEbY7Gjq6BG8xFouUgnWwT74AE3We3o_ReaT3ocU-0S5EupoqEac5ln4bbYaeLlr0wUK0zocB3pO3HfQJPxzPK_Lr5nq9_F7c_bz9sVzcFaDmLBe1Zo1tu0bqzrKqFVLYUjcgQTSylhwaqISsBLSsrECrGpnUyFQ9taTCbi6vyNcDdzs2A7YWfY7Qm210A8SdCeDM6xfvNuYhPBnOFGdVJSfC5yMhht8jpmwGlyz2PXgMYzJCK64YZ3M9RetD1MaQUsTuNIczs5dqJqnmlVRzlDp1P_676Kn51-IUKA-BPeMxjNFP__Yf4GfgNrrN</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2841401078</pqid></control><display><type>article</type><title>Fibroblast Activation Protein-Targeted Photodynamic Therapy of Cancer-Associated Fibroblasts in Murine Models for Pancreatic Ductal Adenocarcinoma</title><source>MEDLINE</source><source>ACS Publications</source><creator>Dorst, Daphne N. ; Smeets, Esther M. M. ; Klein, Christian ; Frielink, Cathelijne ; Geijs, Daan ; Trajkovic-Arsic, Marija ; Cheung, Phyllis F. Y. ; Stommel, Martijn W. J. ; Gotthardt, Martin ; Siveke, Jens T. ; Aarntzen, Erik H. J. G. ; van Lith, Sanne A. M.</creator><creatorcontrib>Dorst, Daphne N. ; Smeets, Esther M. M. ; Klein, Christian ; Frielink, Cathelijne ; Geijs, Daan ; Trajkovic-Arsic, Marija ; Cheung, Phyllis F. Y. ; Stommel, Martijn W. J. ; Gotthardt, Martin ; Siveke, Jens T. ; Aarntzen, Erik H. J. G. ; van Lith, Sanne A. M.</creatorcontrib><description>Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5 year survival of 9%. One important limiting factor for treatment efficacy is the dense tumor-supporting stroma. The cancer-associated fibroblasts in this stroma deposit excessive amounts of extracellular matrix components and anti-inflammatory mediators, which hampers the efficacy of chemo- and immunotherapies. Systemic depletion of all activated fibroblasts is, however, not feasible nor desirable and therefore a local approach should be pursued. Here, we provide a proof-of-principle of using fibroblast activation protein (FAP)-targeted photodynamic therapy (tPDT) to treat PDAC. FAP-targeting antibody 28H1 and irrelevant control antibody DP47GS were conjugated to the photosensitizer IRDye700DX (700DX) and the chelator diethylenetriaminepentaacetic acid. In vitro binding and cytotoxicity were evaluated using the fibroblast cell-line NIH-3T3 stably transfected with FAP. Biodistribution of 111In-labeled antibody-700DX constructs was determined in mice carrying syngeneic tumors of the murine PDAC cell line PDAC299, and in a genetically engineered PDAC mouse model (CKP). Then, tPDT was performed by exposing the subcutaneous or the spontaneous PDAC tumors to 690 nm light. Induction of apoptosis after treatment was assessed using automated analyses of immunohistochemistry for cleaved caspase-3. 28H1-700DX effectively bound to 3T3-FAP cells and induced cytotoxicity upon exposure to 690 nm light, whereas no binding or cytotoxic effects were observed for DP47GS-700DX. Although both 28H1-700DX and DP47GS-700DX accumulated in subcutaneous PDAC299 tumors, autoradiography demonstrated that only 28H1-700DX reached the tumor core. On the contrary, control antibody DP47GS-700DX was only present at the tumor rim. In CKP mice, both antibodies accumulated in the tumor, but tumor-to-blood ratios of 28H1-700DX were higher than that of the control. Notably, in vivo FAP-tPDT caused upregulation of cleaved caspase-3 staining in both subcutaneous and in spontaneous tumors. In conclusion, we have shown that tPDT is a feasible approach for local depletion of FAP-expressing stromal cells in murine models for PDAC.</description><identifier>ISSN: 1543-8384</identifier><identifier>EISSN: 1543-8392</identifier><identifier>DOI: 10.1021/acs.molpharmaceut.3c00453</identifier><identifier>PMID: 37485886</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Antibodies - metabolism ; Cancer-Associated Fibroblasts ; Carcinoma, Pancreatic Ductal - pathology ; Caspase 3 - metabolism ; Cell Line, Tumor ; Disease Models, Animal ; Fibroblasts - metabolism ; Mice ; Pancreatic Neoplasms ; Pancreatic Neoplasms - metabolism ; Photochemotherapy ; Serine Endopeptidases - metabolism ; Tissue Distribution</subject><ispartof>Molecular pharmaceutics, 2023-08, Vol.20 (8), p.4319-4330</ispartof><rights>2023 The Authors. Published by American Chemical Society</rights><rights>2023 The Authors. Published by American Chemical Society 2023 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a470t-980bcdfb38fc06d232c58ba3a2b3931aba62362ad056a849e038e0490bc34ef73</citedby><cites>FETCH-LOGICAL-a470t-980bcdfb38fc06d232c58ba3a2b3931aba62362ad056a849e038e0490bc34ef73</cites><orcidid>0000-0001-8584-2546</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.3c00453$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c00453$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,780,784,885,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37485886$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dorst, Daphne N.</creatorcontrib><creatorcontrib>Smeets, Esther M. M.</creatorcontrib><creatorcontrib>Klein, Christian</creatorcontrib><creatorcontrib>Frielink, Cathelijne</creatorcontrib><creatorcontrib>Geijs, Daan</creatorcontrib><creatorcontrib>Trajkovic-Arsic, Marija</creatorcontrib><creatorcontrib>Cheung, Phyllis F. Y.</creatorcontrib><creatorcontrib>Stommel, Martijn W. J.</creatorcontrib><creatorcontrib>Gotthardt, Martin</creatorcontrib><creatorcontrib>Siveke, Jens T.</creatorcontrib><creatorcontrib>Aarntzen, Erik H. J. G.</creatorcontrib><creatorcontrib>van Lith, Sanne A. M.</creatorcontrib><title>Fibroblast Activation Protein-Targeted Photodynamic Therapy of Cancer-Associated Fibroblasts in Murine Models for Pancreatic Ductal Adenocarcinoma</title><title>Molecular pharmaceutics</title><addtitle>Mol. Pharmaceutics</addtitle><description>Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5 year survival of 9%. One important limiting factor for treatment efficacy is the dense tumor-supporting stroma. The cancer-associated fibroblasts in this stroma deposit excessive amounts of extracellular matrix components and anti-inflammatory mediators, which hampers the efficacy of chemo- and immunotherapies. Systemic depletion of all activated fibroblasts is, however, not feasible nor desirable and therefore a local approach should be pursued. Here, we provide a proof-of-principle of using fibroblast activation protein (FAP)-targeted photodynamic therapy (tPDT) to treat PDAC. FAP-targeting antibody 28H1 and irrelevant control antibody DP47GS were conjugated to the photosensitizer IRDye700DX (700DX) and the chelator diethylenetriaminepentaacetic acid. In vitro binding and cytotoxicity were evaluated using the fibroblast cell-line NIH-3T3 stably transfected with FAP. Biodistribution of 111In-labeled antibody-700DX constructs was determined in mice carrying syngeneic tumors of the murine PDAC cell line PDAC299, and in a genetically engineered PDAC mouse model (CKP). Then, tPDT was performed by exposing the subcutaneous or the spontaneous PDAC tumors to 690 nm light. Induction of apoptosis after treatment was assessed using automated analyses of immunohistochemistry for cleaved caspase-3. 28H1-700DX effectively bound to 3T3-FAP cells and induced cytotoxicity upon exposure to 690 nm light, whereas no binding or cytotoxic effects were observed for DP47GS-700DX. Although both 28H1-700DX and DP47GS-700DX accumulated in subcutaneous PDAC299 tumors, autoradiography demonstrated that only 28H1-700DX reached the tumor core. On the contrary, control antibody DP47GS-700DX was only present at the tumor rim. In CKP mice, both antibodies accumulated in the tumor, but tumor-to-blood ratios of 28H1-700DX were higher than that of the control. Notably, in vivo FAP-tPDT caused upregulation of cleaved caspase-3 staining in both subcutaneous and in spontaneous tumors. In conclusion, we have shown that tPDT is a feasible approach for local depletion of FAP-expressing stromal cells in murine models for PDAC.</description><subject>Animals</subject><subject>Antibodies - metabolism</subject><subject>Cancer-Associated Fibroblasts</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Caspase 3 - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Disease Models, Animal</subject><subject>Fibroblasts - metabolism</subject><subject>Mice</subject><subject>Pancreatic Neoplasms</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Photochemotherapy</subject><subject>Serine Endopeptidases - metabolism</subject><subject>Tissue Distribution</subject><issn>1543-8384</issn><issn>1543-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkctuEzEUhq0KRC_wCsjs2EzwbSaeFYpCW5BakUVYW2c8ZxpXM3awPZXyGjxxJ0pI6Y6VLfn_v3Pkj5BPnM04E_wL2DQbQr_dQBzA4phn0jKmSnlGLnipZKFlLd6c7lqdk8uUHhkTqhTyHTmXc6VLrasL8ufGNTE0PaRMFza7J8gueLqKIaPzxRriA2Zs6WoTcmh3HgZn6XqDEbY7Gjq6BG8xFouUgnWwT74AE3We3o_ReaT3ocU-0S5EupoqEac5ln4bbYaeLlr0wUK0zocB3pO3HfQJPxzPK_Lr5nq9_F7c_bz9sVzcFaDmLBe1Zo1tu0bqzrKqFVLYUjcgQTSylhwaqISsBLSsrECrGpnUyFQ9taTCbi6vyNcDdzs2A7YWfY7Qm210A8SdCeDM6xfvNuYhPBnOFGdVJSfC5yMhht8jpmwGlyz2PXgMYzJCK64YZ3M9RetD1MaQUsTuNIczs5dqJqnmlVRzlDp1P_676Kn51-IUKA-BPeMxjNFP__Yf4GfgNrrN</recordid><startdate>20230807</startdate><enddate>20230807</enddate><creator>Dorst, Daphne N.</creator><creator>Smeets, Esther M. M.</creator><creator>Klein, Christian</creator><creator>Frielink, Cathelijne</creator><creator>Geijs, Daan</creator><creator>Trajkovic-Arsic, Marija</creator><creator>Cheung, Phyllis F. Y.</creator><creator>Stommel, Martijn W. J.</creator><creator>Gotthardt, Martin</creator><creator>Siveke, Jens T.</creator><creator>Aarntzen, Erik H. J. G.</creator><creator>van Lith, Sanne A. M.</creator><general>American Chemical Society</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><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8584-2546</orcidid></search><sort><creationdate>20230807</creationdate><title>Fibroblast Activation Protein-Targeted Photodynamic Therapy of Cancer-Associated Fibroblasts in Murine Models for Pancreatic Ductal Adenocarcinoma</title><author>Dorst, Daphne N. ; Smeets, Esther M. M. ; Klein, Christian ; Frielink, Cathelijne ; Geijs, Daan ; Trajkovic-Arsic, Marija ; Cheung, Phyllis F. Y. ; Stommel, Martijn W. J. ; Gotthardt, Martin ; Siveke, Jens T. ; Aarntzen, Erik H. J. G. ; van Lith, Sanne A. M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a470t-980bcdfb38fc06d232c58ba3a2b3931aba62362ad056a849e038e0490bc34ef73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Antibodies - metabolism</topic><topic>Cancer-Associated Fibroblasts</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Caspase 3 - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Disease Models, Animal</topic><topic>Fibroblasts - metabolism</topic><topic>Mice</topic><topic>Pancreatic Neoplasms</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Photochemotherapy</topic><topic>Serine Endopeptidases - metabolism</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dorst, Daphne N.</creatorcontrib><creatorcontrib>Smeets, Esther M. M.</creatorcontrib><creatorcontrib>Klein, Christian</creatorcontrib><creatorcontrib>Frielink, Cathelijne</creatorcontrib><creatorcontrib>Geijs, Daan</creatorcontrib><creatorcontrib>Trajkovic-Arsic, Marija</creatorcontrib><creatorcontrib>Cheung, Phyllis F. Y.</creatorcontrib><creatorcontrib>Stommel, Martijn W. J.</creatorcontrib><creatorcontrib>Gotthardt, Martin</creatorcontrib><creatorcontrib>Siveke, Jens T.</creatorcontrib><creatorcontrib>Aarntzen, Erik H. J. G.</creatorcontrib><creatorcontrib>van Lith, Sanne A. M.</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dorst, Daphne N.</au><au>Smeets, Esther M. M.</au><au>Klein, Christian</au><au>Frielink, Cathelijne</au><au>Geijs, Daan</au><au>Trajkovic-Arsic, Marija</au><au>Cheung, Phyllis F. Y.</au><au>Stommel, Martijn W. J.</au><au>Gotthardt, Martin</au><au>Siveke, Jens T.</au><au>Aarntzen, Erik H. J. G.</au><au>van Lith, Sanne A. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fibroblast Activation Protein-Targeted Photodynamic Therapy of Cancer-Associated Fibroblasts in Murine Models for Pancreatic Ductal Adenocarcinoma</atitle><jtitle>Molecular pharmaceutics</jtitle><addtitle>Mol. Pharmaceutics</addtitle><date>2023-08-07</date><risdate>2023</risdate><volume>20</volume><issue>8</issue><spage>4319</spage><epage>4330</epage><pages>4319-4330</pages><issn>1543-8384</issn><eissn>1543-8392</eissn><abstract>Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5 year survival of 9%. One important limiting factor for treatment efficacy is the dense tumor-supporting stroma. The cancer-associated fibroblasts in this stroma deposit excessive amounts of extracellular matrix components and anti-inflammatory mediators, which hampers the efficacy of chemo- and immunotherapies. Systemic depletion of all activated fibroblasts is, however, not feasible nor desirable and therefore a local approach should be pursued. Here, we provide a proof-of-principle of using fibroblast activation protein (FAP)-targeted photodynamic therapy (tPDT) to treat PDAC. FAP-targeting antibody 28H1 and irrelevant control antibody DP47GS were conjugated to the photosensitizer IRDye700DX (700DX) and the chelator diethylenetriaminepentaacetic acid. In vitro binding and cytotoxicity were evaluated using the fibroblast cell-line NIH-3T3 stably transfected with FAP. Biodistribution of 111In-labeled antibody-700DX constructs was determined in mice carrying syngeneic tumors of the murine PDAC cell line PDAC299, and in a genetically engineered PDAC mouse model (CKP). Then, tPDT was performed by exposing the subcutaneous or the spontaneous PDAC tumors to 690 nm light. Induction of apoptosis after treatment was assessed using automated analyses of immunohistochemistry for cleaved caspase-3. 28H1-700DX effectively bound to 3T3-FAP cells and induced cytotoxicity upon exposure to 690 nm light, whereas no binding or cytotoxic effects were observed for DP47GS-700DX. Although both 28H1-700DX and DP47GS-700DX accumulated in subcutaneous PDAC299 tumors, autoradiography demonstrated that only 28H1-700DX reached the tumor core. On the contrary, control antibody DP47GS-700DX was only present at the tumor rim. In CKP mice, both antibodies accumulated in the tumor, but tumor-to-blood ratios of 28H1-700DX were higher than that of the control. Notably, in vivo FAP-tPDT caused upregulation of cleaved caspase-3 staining in both subcutaneous and in spontaneous tumors. In conclusion, we have shown that tPDT is a feasible approach for local depletion of FAP-expressing stromal cells in murine models for PDAC.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>37485886</pmid><doi>10.1021/acs.molpharmaceut.3c00453</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8584-2546</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1543-8384
ispartof Molecular pharmaceutics, 2023-08, Vol.20 (8), p.4319-4330
issn 1543-8384
1543-8392
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10410663
source MEDLINE; ACS Publications
subjects Animals
Antibodies - metabolism
Cancer-Associated Fibroblasts
Carcinoma, Pancreatic Ductal - pathology
Caspase 3 - metabolism
Cell Line, Tumor
Disease Models, Animal
Fibroblasts - metabolism
Mice
Pancreatic Neoplasms
Pancreatic Neoplasms - metabolism
Photochemotherapy
Serine Endopeptidases - metabolism
Tissue Distribution
title Fibroblast Activation Protein-Targeted Photodynamic Therapy of Cancer-Associated Fibroblasts in Murine Models for Pancreatic Ductal Adenocarcinoma
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T05%3A31%3A27IST&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=Fibroblast%20Activation%20Protein-Targeted%20Photodynamic%20Therapy%20of%20Cancer-Associated%20Fibroblasts%20in%20Murine%20Models%20for%20Pancreatic%20Ductal%20Adenocarcinoma&rft.jtitle=Molecular%20pharmaceutics&rft.au=Dorst,%20Daphne%20N.&rft.date=2023-08-07&rft.volume=20&rft.issue=8&rft.spage=4319&rft.epage=4330&rft.pages=4319-4330&rft.issn=1543-8384&rft.eissn=1543-8392&rft_id=info:doi/10.1021/acs.molpharmaceut.3c00453&rft_dat=%3Cproquest_pubme%3E2841401078%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2841401078&rft_id=info:pmid/37485886&rfr_iscdi=true