Supramolecular Crafting of Self-Assembling Camptothecin Prodrugs with Enhanced Efficacy against Primary Cancer Cells
Chemical modification of small molecule hydrophobic drugs is a clinically proven strategy to devise prodrugs with enhanced treatment efficacy. While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency ag...
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| Veröffentlicht in: | Theranostics 2016-01, Vol.6 (7), p.1065-1074 |
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| container_title | Theranostics |
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| creator | Su, Hao Zhang, Pengcheng Cheetham, Andrew G Koo, Jin Mo Lin, Ran Masood, Asad Schiapparelli, Paula Quiñones-Hinojosa, Alfredo Cui, Honggang |
| description | Chemical modification of small molecule hydrophobic drugs is a clinically proven strategy to devise prodrugs with enhanced treatment efficacy. While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency against cancer cells due to the retarded drug release rate and reduced cellular uptake efficiency. Here we report on the supramolecular design of self-assembling prodrugs (SAPD) with much improved water solubility while maintaining high potency against cancer cells. We found that camptothecin (CPT) prodrugs created by conjugating two CPT molecules onto a hydrophilic segment can associate into filamentous nanostructures in water. Our results suggest that these SAPD exhibit much greater efficacy against primary brain cancer cells relative to that of irinotecan, a clinically used CPT prodrug. We believe these findings open a new avenue for rational design of supramolecular prodrugs for cancer treatment. |
| doi_str_mv | 10.7150/thno.15420 |
| format | Article |
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While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency against cancer cells due to the retarded drug release rate and reduced cellular uptake efficiency. Here we report on the supramolecular design of self-assembling prodrugs (SAPD) with much improved water solubility while maintaining high potency against cancer cells. We found that camptothecin (CPT) prodrugs created by conjugating two CPT molecules onto a hydrophilic segment can associate into filamentous nanostructures in water. Our results suggest that these SAPD exhibit much greater efficacy against primary brain cancer cells relative to that of irinotecan, a clinically used CPT prodrug. We believe these findings open a new avenue for rational design of supramolecular prodrugs for cancer treatment.</description><identifier>ISSN: 1838-7640</identifier><identifier>EISSN: 1838-7640</identifier><identifier>DOI: 10.7150/thno.15420</identifier><identifier>PMID: 27217839</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher</publisher><subject>Antineoplastic Agents, Phytogenic - chemical synthesis ; Antineoplastic Agents, Phytogenic - chemistry ; Antineoplastic Agents, Phytogenic - pharmacology ; Brain Neoplasms ; Camptothecin - chemical synthesis ; Camptothecin - chemistry ; Camptothecin - pharmacology ; Cell Line, Tumor ; Cell Survival - drug effects ; Humans ; Prodrugs - chemical synthesis ; Prodrugs - chemistry ; Prodrugs - pharmacology ; Research Paper ; Solubility</subject><ispartof>Theranostics, 2016-01, Vol.6 (7), p.1065-1074</ispartof><rights>Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-640d3b6be86b97d3a3bfdafdc9da1c9a4461dda9fd098997bea9f4ef64bdead33</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/PMC4876630/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876630/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27217839$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Su, Hao</creatorcontrib><creatorcontrib>Zhang, Pengcheng</creatorcontrib><creatorcontrib>Cheetham, Andrew G</creatorcontrib><creatorcontrib>Koo, Jin Mo</creatorcontrib><creatorcontrib>Lin, Ran</creatorcontrib><creatorcontrib>Masood, Asad</creatorcontrib><creatorcontrib>Schiapparelli, Paula</creatorcontrib><creatorcontrib>Quiñones-Hinojosa, Alfredo</creatorcontrib><creatorcontrib>Cui, Honggang</creatorcontrib><title>Supramolecular Crafting of Self-Assembling Camptothecin Prodrugs with Enhanced Efficacy against Primary Cancer Cells</title><title>Theranostics</title><addtitle>Theranostics</addtitle><description>Chemical modification of small molecule hydrophobic drugs is a clinically proven strategy to devise prodrugs with enhanced treatment efficacy. While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency against cancer cells due to the retarded drug release rate and reduced cellular uptake efficiency. Here we report on the supramolecular design of self-assembling prodrugs (SAPD) with much improved water solubility while maintaining high potency against cancer cells. We found that camptothecin (CPT) prodrugs created by conjugating two CPT molecules onto a hydrophilic segment can associate into filamentous nanostructures in water. Our results suggest that these SAPD exhibit much greater efficacy against primary brain cancer cells relative to that of irinotecan, a clinically used CPT prodrug. We believe these findings open a new avenue for rational design of supramolecular prodrugs for cancer treatment.</description><subject>Antineoplastic Agents, Phytogenic - chemical synthesis</subject><subject>Antineoplastic Agents, Phytogenic - chemistry</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Brain Neoplasms</subject><subject>Camptothecin - chemical synthesis</subject><subject>Camptothecin - chemistry</subject><subject>Camptothecin - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Humans</subject><subject>Prodrugs - chemical synthesis</subject><subject>Prodrugs - chemistry</subject><subject>Prodrugs - pharmacology</subject><subject>Research Paper</subject><subject>Solubility</subject><issn>1838-7640</issn><issn>1838-7640</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUNtKw0AQXUSxpfbFD5A8C6m72TTJvggl1AsUFKrPYbKXZCU3djdK_96t1VLnZQ4z55wZDkLXBC9SssR3ru76BVnGET5DU5LRLEyTGJ-f4AmaW_uBfcU4YoRdokmURiTNKJsitx0HA23fSD42YILcgHK6q4JeBVvZqHBlrWzLZj_KoR1c72rJdRe8ml6YsbLBl3Z1sO5q6LgUwVopzYHvAqhAd9Z5nm7B7LzY772_bBp7hS4UNFbOf_sMvT-s3_KncPPy-JyvNiGnaeZC_7ugZVLKLClZKijQUglQgjMBhDOI44QIAUwJzDLG0lJ6HEuVxKWQICidofuD7zCWrRRcds5AUwyHl4oedPF_0-m6qPrPIs7SJKHYG9weDLjprTVSHbUEF_v4i338xU_8nnxzeu1I_QubfgOIYoYF</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Su, Hao</creator><creator>Zhang, Pengcheng</creator><creator>Cheetham, Andrew G</creator><creator>Koo, Jin Mo</creator><creator>Lin, Ran</creator><creator>Masood, Asad</creator><creator>Schiapparelli, Paula</creator><creator>Quiñones-Hinojosa, Alfredo</creator><creator>Cui, Honggang</creator><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>5PM</scope></search><sort><creationdate>20160101</creationdate><title>Supramolecular Crafting of Self-Assembling Camptothecin Prodrugs with Enhanced Efficacy against Primary Cancer Cells</title><author>Su, Hao ; Zhang, Pengcheng ; Cheetham, Andrew G ; Koo, Jin Mo ; Lin, Ran ; Masood, Asad ; Schiapparelli, Paula ; Quiñones-Hinojosa, Alfredo ; Cui, Honggang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-640d3b6be86b97d3a3bfdafdc9da1c9a4461dda9fd098997bea9f4ef64bdead33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Antineoplastic Agents, Phytogenic - chemical synthesis</topic><topic>Antineoplastic Agents, Phytogenic - chemistry</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Brain Neoplasms</topic><topic>Camptothecin - chemical synthesis</topic><topic>Camptothecin - chemistry</topic><topic>Camptothecin - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Humans</topic><topic>Prodrugs - chemical synthesis</topic><topic>Prodrugs - chemistry</topic><topic>Prodrugs - pharmacology</topic><topic>Research Paper</topic><topic>Solubility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Hao</creatorcontrib><creatorcontrib>Zhang, Pengcheng</creatorcontrib><creatorcontrib>Cheetham, Andrew G</creatorcontrib><creatorcontrib>Koo, Jin Mo</creatorcontrib><creatorcontrib>Lin, Ran</creatorcontrib><creatorcontrib>Masood, Asad</creatorcontrib><creatorcontrib>Schiapparelli, Paula</creatorcontrib><creatorcontrib>Quiñones-Hinojosa, Alfredo</creatorcontrib><creatorcontrib>Cui, Honggang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Theranostics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Su, Hao</au><au>Zhang, Pengcheng</au><au>Cheetham, Andrew G</au><au>Koo, Jin Mo</au><au>Lin, Ran</au><au>Masood, Asad</au><au>Schiapparelli, Paula</au><au>Quiñones-Hinojosa, Alfredo</au><au>Cui, Honggang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Supramolecular Crafting of Self-Assembling Camptothecin Prodrugs with Enhanced Efficacy against Primary Cancer Cells</atitle><jtitle>Theranostics</jtitle><addtitle>Theranostics</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>6</volume><issue>7</issue><spage>1065</spage><epage>1074</epage><pages>1065-1074</pages><issn>1838-7640</issn><eissn>1838-7640</eissn><abstract>Chemical modification of small molecule hydrophobic drugs is a clinically proven strategy to devise prodrugs with enhanced treatment efficacy. While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency against cancer cells due to the retarded drug release rate and reduced cellular uptake efficiency. Here we report on the supramolecular design of self-assembling prodrugs (SAPD) with much improved water solubility while maintaining high potency against cancer cells. We found that camptothecin (CPT) prodrugs created by conjugating two CPT molecules onto a hydrophilic segment can associate into filamentous nanostructures in water. Our results suggest that these SAPD exhibit much greater efficacy against primary brain cancer cells relative to that of irinotecan, a clinically used CPT prodrug. We believe these findings open a new avenue for rational design of supramolecular prodrugs for cancer treatment.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher</pub><pmid>27217839</pmid><doi>10.7150/thno.15420</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Theranostics, 2016-01, Vol.6 (7), p.1065-1074 |
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| subjects | Antineoplastic Agents, Phytogenic - chemical synthesis Antineoplastic Agents, Phytogenic - chemistry Antineoplastic Agents, Phytogenic - pharmacology Brain Neoplasms Camptothecin - chemical synthesis Camptothecin - chemistry Camptothecin - pharmacology Cell Line, Tumor Cell Survival - drug effects Humans Prodrugs - chemical synthesis Prodrugs - chemistry Prodrugs - pharmacology Research Paper Solubility |
| title | Supramolecular Crafting of Self-Assembling Camptothecin Prodrugs with Enhanced Efficacy against Primary Cancer Cells |
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