Tuned near infrared fluorescent hyaluronic acid conjugates for delivery to pancreatic cancer for intraoperative imaging
The prognosis of pancreatic cancer remains poor. Intraoperative fluorescence imaging of tumors could improve staging and surgical resection, thereby improving prognosis. However, imaging pancreatic cancer with macromolecular delivery systems, is often hampered by nonspecific organ accumulation. : We...
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| Veröffentlicht in: | Theranostics 2020-01, Vol.10 (8), p.3413-3429 |
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| creator | Qi, Bowen Crawford, Ayrianne J Wojtynek, Nicholas E Talmon, Geoffrey A Hollingsworth, Michael A Ly, Quan P Mohs, Aaron M |
| description | The prognosis of pancreatic cancer remains poor. Intraoperative fluorescence imaging of tumors could improve staging and surgical resection, thereby improving prognosis. However, imaging pancreatic cancer with macromolecular delivery systems, is often hampered by nonspecific organ accumulation.
: We describe the rational development of hyaluronic acid (HA) conjugates that vary in molecular weight and are conjugated to near infrared fluorescent (NIRF) dyes that have differences in hydrophilicity, serum protein binding affinity, and clearance mechanism. We systematically investigated the roles of each of these properties on tumor accumulation, relative biodistribution, and the impact of intraoperative imaging of orthotopic, syngeneic pancreatic cancer.
: Each HA-NIRF conjugate displayed intrapancreatic tumor enhancement. Regardless of HA molecular weight, Cy7.5 conjugation directed biodistribution to the liver, spleen, and bowels. Conjugation of IRDye800 to 5 and 20 kDa HA resulted in low liver and spleen signal while enhancing the tumor up to 14-fold compared to healthy pancreas, while 100 kDa HA conjugated to IRDye800 resulting in liver and spleen accumulation.
: These studies demonstrate that by tuning HA molecular weight and the physicochemical properties of the conjugated moiety, in this case a NIRF probe, peritoneal biodistribution can be substantially altered to achieve optimized delivery to tumors intraoperative abdominal imaging. |
| doi_str_mv | 10.7150/thno.40688 |
| format | Article |
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: We describe the rational development of hyaluronic acid (HA) conjugates that vary in molecular weight and are conjugated to near infrared fluorescent (NIRF) dyes that have differences in hydrophilicity, serum protein binding affinity, and clearance mechanism. We systematically investigated the roles of each of these properties on tumor accumulation, relative biodistribution, and the impact of intraoperative imaging of orthotopic, syngeneic pancreatic cancer.
: Each HA-NIRF conjugate displayed intrapancreatic tumor enhancement. Regardless of HA molecular weight, Cy7.5 conjugation directed biodistribution to the liver, spleen, and bowels. Conjugation of IRDye800 to 5 and 20 kDa HA resulted in low liver and spleen signal while enhancing the tumor up to 14-fold compared to healthy pancreas, while 100 kDa HA conjugated to IRDye800 resulting in liver and spleen accumulation.
: These studies demonstrate that by tuning HA molecular weight and the physicochemical properties of the conjugated moiety, in this case a NIRF probe, peritoneal biodistribution can be substantially altered to achieve optimized delivery to tumors intraoperative abdominal imaging.</description><identifier>ISSN: 1838-7640</identifier><identifier>EISSN: 1838-7640</identifier><identifier>DOI: 10.7150/thno.40688</identifier><identifier>PMID: 32206099</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher Pty Ltd</publisher><subject>Adenocarcinoma - diagnostic imaging ; Adenocarcinoma - surgery ; Aggregates ; Animals ; Chromatography ; Contrast agents ; Contrast Media - administration & dosage ; Contrast Media - chemistry ; Drug Delivery Systems ; Dyes ; Female ; Fluorescent Dyes - administration & dosage ; Fluorescent Dyes - chemistry ; Hyaluronic Acid - administration & dosage ; Hyaluronic Acid - chemistry ; Intraoperative Care ; Metastasis ; Mice, Inbred C57BL ; Molecular Structure ; Noise ; Optical properties ; Pancreatic cancer ; Pancreatic Neoplasms - diagnostic imaging ; Pancreatic Neoplasms - surgery ; Pharmacokinetics ; Proteins ; Research Paper ; Serum Albumin, Bovine ; Tumors</subject><ispartof>Theranostics, 2020-01, Vol.10 (8), p.3413-3429</ispartof><rights>The author(s).</rights><rights>2020. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-28019b4f3cae1278471a84ac839e7c396609be715e045bcb254a978554be47d43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069077/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069077/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53768,53770</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32206099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qi, Bowen</creatorcontrib><creatorcontrib>Crawford, Ayrianne J</creatorcontrib><creatorcontrib>Wojtynek, Nicholas E</creatorcontrib><creatorcontrib>Talmon, Geoffrey A</creatorcontrib><creatorcontrib>Hollingsworth, Michael A</creatorcontrib><creatorcontrib>Ly, Quan P</creatorcontrib><creatorcontrib>Mohs, Aaron M</creatorcontrib><title>Tuned near infrared fluorescent hyaluronic acid conjugates for delivery to pancreatic cancer for intraoperative imaging</title><title>Theranostics</title><addtitle>Theranostics</addtitle><description>The prognosis of pancreatic cancer remains poor. Intraoperative fluorescence imaging of tumors could improve staging and surgical resection, thereby improving prognosis. However, imaging pancreatic cancer with macromolecular delivery systems, is often hampered by nonspecific organ accumulation.
: We describe the rational development of hyaluronic acid (HA) conjugates that vary in molecular weight and are conjugated to near infrared fluorescent (NIRF) dyes that have differences in hydrophilicity, serum protein binding affinity, and clearance mechanism. We systematically investigated the roles of each of these properties on tumor accumulation, relative biodistribution, and the impact of intraoperative imaging of orthotopic, syngeneic pancreatic cancer.
: Each HA-NIRF conjugate displayed intrapancreatic tumor enhancement. Regardless of HA molecular weight, Cy7.5 conjugation directed biodistribution to the liver, spleen, and bowels. Conjugation of IRDye800 to 5 and 20 kDa HA resulted in low liver and spleen signal while enhancing the tumor up to 14-fold compared to healthy pancreas, while 100 kDa HA conjugated to IRDye800 resulting in liver and spleen accumulation.
: These studies demonstrate that by tuning HA molecular weight and the physicochemical properties of the conjugated moiety, in this case a NIRF probe, peritoneal biodistribution can be substantially altered to achieve optimized delivery to tumors intraoperative abdominal imaging.</description><subject>Adenocarcinoma - diagnostic imaging</subject><subject>Adenocarcinoma - surgery</subject><subject>Aggregates</subject><subject>Animals</subject><subject>Chromatography</subject><subject>Contrast agents</subject><subject>Contrast Media - administration & dosage</subject><subject>Contrast Media - chemistry</subject><subject>Drug Delivery Systems</subject><subject>Dyes</subject><subject>Female</subject><subject>Fluorescent Dyes - administration & dosage</subject><subject>Fluorescent Dyes - chemistry</subject><subject>Hyaluronic Acid - administration & dosage</subject><subject>Hyaluronic Acid - chemistry</subject><subject>Intraoperative Care</subject><subject>Metastasis</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Structure</subject><subject>Noise</subject><subject>Optical properties</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - diagnostic imaging</subject><subject>Pancreatic Neoplasms - surgery</subject><subject>Pharmacokinetics</subject><subject>Proteins</subject><subject>Research Paper</subject><subject>Serum Albumin, Bovine</subject><subject>Tumors</subject><issn>1838-7640</issn><issn>1838-7640</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkU1rGzEQhkVoaUKaS35AEPRSCk70tSvpUiihH4FALslZaLWztsxacke7Lv73lZM0pNFFM8zD8L7zEnLO2aXmDbuaVilfKtYac0ROuJFmoVvF3r2qj8lZKWtWn2LCcvuBHEshWMusPSF_7ucEPU3gkcY0oMfaDeOcEUqANNHV3o8z5hQD9SH2NOS0npd-gkKHjLSHMe4A93TKdOtTQPBTRUMtAR-JmCb0eQtYBzugceOXMS0_kveDHwucPf-n5OHH9_vrX4vbu583199uF6F6mhbCMG47NcjggQttlObeKB-MtKCDtG110UE9BDDVdKETjfJWm6ZRHSjdK3lKvj7t3c7dBvqDJfSj22LVgXuXfXT_T1JcuWXeOc1ay7SuCz4_L8D8e4YyuU2slxlHnyDPxQlpRNtyZVhFP71B13nGVO050VgjGtlaWakvT1TAXArC8CKGM3eI1B0idY-RVvjitfwX9F-A8i9mF58m</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Qi, Bowen</creator><creator>Crawford, Ayrianne J</creator><creator>Wojtynek, Nicholas E</creator><creator>Talmon, Geoffrey A</creator><creator>Hollingsworth, Michael A</creator><creator>Ly, Quan P</creator><creator>Mohs, Aaron M</creator><general>Ivyspring International Publisher Pty Ltd</general><general>Ivyspring International Publisher</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200101</creationdate><title>Tuned near infrared fluorescent hyaluronic acid conjugates for delivery to pancreatic cancer for intraoperative imaging</title><author>Qi, Bowen ; Crawford, Ayrianne J ; Wojtynek, Nicholas E ; Talmon, Geoffrey A ; Hollingsworth, Michael A ; Ly, Quan P ; Mohs, Aaron M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-28019b4f3cae1278471a84ac839e7c396609be715e045bcb254a978554be47d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenocarcinoma - diagnostic imaging</topic><topic>Adenocarcinoma - surgery</topic><topic>Aggregates</topic><topic>Animals</topic><topic>Chromatography</topic><topic>Contrast agents</topic><topic>Contrast Media - administration & dosage</topic><topic>Contrast Media - chemistry</topic><topic>Drug Delivery Systems</topic><topic>Dyes</topic><topic>Female</topic><topic>Fluorescent Dyes - administration & dosage</topic><topic>Fluorescent Dyes - chemistry</topic><topic>Hyaluronic Acid - administration & dosage</topic><topic>Hyaluronic Acid - chemistry</topic><topic>Intraoperative Care</topic><topic>Metastasis</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Structure</topic><topic>Noise</topic><topic>Optical properties</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - diagnostic imaging</topic><topic>Pancreatic Neoplasms - surgery</topic><topic>Pharmacokinetics</topic><topic>Proteins</topic><topic>Research Paper</topic><topic>Serum Albumin, Bovine</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qi, Bowen</creatorcontrib><creatorcontrib>Crawford, Ayrianne J</creatorcontrib><creatorcontrib>Wojtynek, Nicholas E</creatorcontrib><creatorcontrib>Talmon, Geoffrey A</creatorcontrib><creatorcontrib>Hollingsworth, Michael A</creatorcontrib><creatorcontrib>Ly, Quan P</creatorcontrib><creatorcontrib>Mohs, Aaron 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>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Theranostics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qi, Bowen</au><au>Crawford, Ayrianne J</au><au>Wojtynek, Nicholas E</au><au>Talmon, Geoffrey A</au><au>Hollingsworth, Michael A</au><au>Ly, Quan P</au><au>Mohs, Aaron M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tuned near infrared fluorescent hyaluronic acid conjugates for delivery to pancreatic cancer for intraoperative imaging</atitle><jtitle>Theranostics</jtitle><addtitle>Theranostics</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>10</volume><issue>8</issue><spage>3413</spage><epage>3429</epage><pages>3413-3429</pages><issn>1838-7640</issn><eissn>1838-7640</eissn><abstract>The prognosis of pancreatic cancer remains poor. Intraoperative fluorescence imaging of tumors could improve staging and surgical resection, thereby improving prognosis. However, imaging pancreatic cancer with macromolecular delivery systems, is often hampered by nonspecific organ accumulation.
: We describe the rational development of hyaluronic acid (HA) conjugates that vary in molecular weight and are conjugated to near infrared fluorescent (NIRF) dyes that have differences in hydrophilicity, serum protein binding affinity, and clearance mechanism. We systematically investigated the roles of each of these properties on tumor accumulation, relative biodistribution, and the impact of intraoperative imaging of orthotopic, syngeneic pancreatic cancer.
: Each HA-NIRF conjugate displayed intrapancreatic tumor enhancement. Regardless of HA molecular weight, Cy7.5 conjugation directed biodistribution to the liver, spleen, and bowels. Conjugation of IRDye800 to 5 and 20 kDa HA resulted in low liver and spleen signal while enhancing the tumor up to 14-fold compared to healthy pancreas, while 100 kDa HA conjugated to IRDye800 resulting in liver and spleen accumulation.
: These studies demonstrate that by tuning HA molecular weight and the physicochemical properties of the conjugated moiety, in this case a NIRF probe, peritoneal biodistribution can be substantially altered to achieve optimized delivery to tumors intraoperative abdominal imaging.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>32206099</pmid><doi>10.7150/thno.40688</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma - diagnostic imaging Adenocarcinoma - surgery Aggregates Animals Chromatography Contrast agents Contrast Media - administration & dosage Contrast Media - chemistry Drug Delivery Systems Dyes Female Fluorescent Dyes - administration & dosage Fluorescent Dyes - chemistry Hyaluronic Acid - administration & dosage Hyaluronic Acid - chemistry Intraoperative Care Metastasis Mice, Inbred C57BL Molecular Structure Noise Optical properties Pancreatic cancer Pancreatic Neoplasms - diagnostic imaging Pancreatic Neoplasms - surgery Pharmacokinetics Proteins Research Paper Serum Albumin, Bovine Tumors |
| title | Tuned near infrared fluorescent hyaluronic acid conjugates for delivery to pancreatic cancer for intraoperative imaging |
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