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A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site
We demonstrate that Dz13, a DNA enzyme that cleaves c-Jun mRNA, and is capable of inhibiting cancer cell growth in vitro, can be encapsulated into chitosan nanoparticles. For optimisation of this chitosan-based formulation, pH 6, 0.02% chitosan concentration, and 55 °C were found to be best among th...
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Published in: | Journal of controlled release 2010-06, Vol.144 (2), p.196-202 |
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creator | Tan, Mei Lin Dunstan, Dave E. Friedhuber, Anna M. Choong, Peter F.M. Dass, Crispin R. |
description | We demonstrate that Dz13, a DNA enzyme that cleaves c-Jun mRNA, and is capable of inhibiting cancer cell growth in vitro, can be encapsulated into chitosan nanoparticles. For optimisation of this chitosan-based formulation, pH 6, 0.02% chitosan concentration, and 55
°C were found to be best among the variables tested. Particles were 50–300
nm in diameter and encapsulated Dz13 was active when particles were exposed to cancer cells. Nanoparticles were stable during storage even for a month, but were not stable in mouse and human serum. In two different clinically-relevant disease models, and using a clinically-adoptable dosing regimen, these Dz13-nanoparticles were shown to be efficacious against a bone tumour (osteosarcoma), for which no real cure exists currently. However, no toxicity against other bone-dwelling cells was observed with the formulation, and no side-effects were noted in vivo in lymphatic and reticuloendothelial tissues proximal and distal to the administration site.
Nanoencapsulated Dz13 with enhanced tumoricidal effect. Tumour cell changes from normal (left) to treated (right) include nuclear (
n) fragmentation, chromatin (
c) condensation, mitochondrial (
m) breakage, and plasma membrane (
p) blebbing.
[Display omitted] |
doi_str_mv | 10.1016/j.jconrel.2010.01.011 |
format | article |
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°C were found to be best among the variables tested. Particles were 50–300
nm in diameter and encapsulated Dz13 was active when particles were exposed to cancer cells. Nanoparticles were stable during storage even for a month, but were not stable in mouse and human serum. In two different clinically-relevant disease models, and using a clinically-adoptable dosing regimen, these Dz13-nanoparticles were shown to be efficacious against a bone tumour (osteosarcoma), for which no real cure exists currently. However, no toxicity against other bone-dwelling cells was observed with the formulation, and no side-effects were noted in vivo in lymphatic and reticuloendothelial tissues proximal and distal to the administration site.
Nanoencapsulated Dz13 with enhanced tumoricidal effect. Tumour cell changes from normal (left) to treated (right) include nuclear (
n) fragmentation, chromatin (
c) condensation, mitochondrial (
m) breakage, and plasma membrane (
p) blebbing.
[Display omitted]</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2010.01.011</identifier><identifier>PMID: 20079783</identifier><identifier>CODEN: JCREEC</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>Animals ; Antisense ; Biological and medical sciences ; Bone Neoplasms - therapy ; Cancer ; Chitosan ; Chitosan - chemistry ; DNA - chemistry ; DNAzyme ; General pharmacology ; Humans ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nanoparticle ; Nanoparticles - therapeutic use ; Osteosarcoma - therapy ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Tumour</subject><ispartof>Journal of controlled release, 2010-06, Vol.144 (2), p.196-202</ispartof><rights>2010 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright (c) 2010 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-63e94c9b7c0f1c11f08f0fa6a3e3e5b5a4ac869466bad3a72ef053945363ef1a3</citedby><cites>FETCH-LOGICAL-c426t-63e94c9b7c0f1c11f08f0fa6a3e3e5b5a4ac869466bad3a72ef053945363ef1a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22830943$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20079783$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tan, Mei Lin</creatorcontrib><creatorcontrib>Dunstan, Dave E.</creatorcontrib><creatorcontrib>Friedhuber, Anna M.</creatorcontrib><creatorcontrib>Choong, Peter F.M.</creatorcontrib><creatorcontrib>Dass, Crispin R.</creatorcontrib><title>A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>We demonstrate that Dz13, a DNA enzyme that cleaves c-Jun mRNA, and is capable of inhibiting cancer cell growth in vitro, can be encapsulated into chitosan nanoparticles. For optimisation of this chitosan-based formulation, pH 6, 0.02% chitosan concentration, and 55
°C were found to be best among the variables tested. Particles were 50–300
nm in diameter and encapsulated Dz13 was active when particles were exposed to cancer cells. Nanoparticles were stable during storage even for a month, but were not stable in mouse and human serum. In two different clinically-relevant disease models, and using a clinically-adoptable dosing regimen, these Dz13-nanoparticles were shown to be efficacious against a bone tumour (osteosarcoma), for which no real cure exists currently. However, no toxicity against other bone-dwelling cells was observed with the formulation, and no side-effects were noted in vivo in lymphatic and reticuloendothelial tissues proximal and distal to the administration site.
Nanoencapsulated Dz13 with enhanced tumoricidal effect. Tumour cell changes from normal (left) to treated (right) include nuclear (
n) fragmentation, chromatin (
c) condensation, mitochondrial (
m) breakage, and plasma membrane (
p) blebbing.
[Display omitted]</description><subject>Animals</subject><subject>Antisense</subject><subject>Biological and medical sciences</subject><subject>Bone Neoplasms - therapy</subject><subject>Cancer</subject><subject>Chitosan</subject><subject>Chitosan - chemistry</subject><subject>DNA - chemistry</subject><subject>DNAzyme</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Nanoparticle</subject><subject>Nanoparticles - therapeutic use</subject><subject>Osteosarcoma - therapy</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Tumour</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqFkE2PFCEQhonRuOPqT9BwMXvqERqabk5ms-tXsokXPZMausgw6YYRaHfHXy-zM-rRpBJS5HmL4iHkNWdrzrh6t1vvbAwJp3XL6h3jtfgTsuJDLxqpdfeUrCo3NEJ1-oK8yHnHGOuE7J-Ti5axXveDWJGHaxogxD2k4u0yQUGaD7ngTMsWCsWwhWAx1w4pOuct2AON7rEvyxyTt35EevuLC3q_xUBhnH3wdULCke5TfPAzTLTEx8SE2cdAsy_4kjxzMGV8dT4vyfePH77dfG7uvn76cnN911jZqtIogVpavektc9xy7tjgmAMFAgV2mw4k2EFpqdQGRgF9i65-UstO1KTjIC7J1Wlu3eXHgrmY2WeL0wQB45JNLzsl1NCKSnYn0qaYc0Jn9qkunw6GM3N0bnbm7NwcnRvGa_Gae3N-YdnMOP5N_ZFcgbdnALKFyaWq1Od_XDsIpuWRe3_isPr46TGZbD1W_aNPaIsZo__PKr8Bfi6kJg</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Tan, Mei Lin</creator><creator>Dunstan, Dave E.</creator><creator>Friedhuber, Anna M.</creator><creator>Choong, Peter F.M.</creator><creator>Dass, Crispin R.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20100601</creationdate><title>A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site</title><author>Tan, Mei Lin ; Dunstan, Dave E. ; Friedhuber, Anna M. ; Choong, Peter F.M. ; Dass, Crispin R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-63e94c9b7c0f1c11f08f0fa6a3e3e5b5a4ac869466bad3a72ef053945363ef1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antisense</topic><topic>Biological and medical sciences</topic><topic>Bone Neoplasms - therapy</topic><topic>Cancer</topic><topic>Chitosan</topic><topic>Chitosan - chemistry</topic><topic>DNA - chemistry</topic><topic>DNAzyme</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Nanoparticle</topic><topic>Nanoparticles - therapeutic use</topic><topic>Osteosarcoma - therapy</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Tumour</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tan, Mei Lin</creatorcontrib><creatorcontrib>Dunstan, Dave E.</creatorcontrib><creatorcontrib>Friedhuber, Anna M.</creatorcontrib><creatorcontrib>Choong, Peter F.M.</creatorcontrib><creatorcontrib>Dass, Crispin R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tan, Mei Lin</au><au>Dunstan, Dave E.</au><au>Friedhuber, Anna M.</au><au>Choong, Peter F.M.</au><au>Dass, Crispin R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>144</volume><issue>2</issue><spage>196</spage><epage>202</epage><pages>196-202</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><coden>JCREEC</coden><abstract>We demonstrate that Dz13, a DNA enzyme that cleaves c-Jun mRNA, and is capable of inhibiting cancer cell growth in vitro, can be encapsulated into chitosan nanoparticles. For optimisation of this chitosan-based formulation, pH 6, 0.02% chitosan concentration, and 55
°C were found to be best among the variables tested. Particles were 50–300
nm in diameter and encapsulated Dz13 was active when particles were exposed to cancer cells. Nanoparticles were stable during storage even for a month, but were not stable in mouse and human serum. In two different clinically-relevant disease models, and using a clinically-adoptable dosing regimen, these Dz13-nanoparticles were shown to be efficacious against a bone tumour (osteosarcoma), for which no real cure exists currently. However, no toxicity against other bone-dwelling cells was observed with the formulation, and no side-effects were noted in vivo in lymphatic and reticuloendothelial tissues proximal and distal to the administration site.
Nanoencapsulated Dz13 with enhanced tumoricidal effect. Tumour cell changes from normal (left) to treated (right) include nuclear (
n) fragmentation, chromatin (
c) condensation, mitochondrial (
m) breakage, and plasma membrane (
p) blebbing.
[Display omitted]</abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>20079783</pmid><doi>10.1016/j.jconrel.2010.01.011</doi><tpages>7</tpages></addata></record> |
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subjects | Animals Antisense Biological and medical sciences Bone Neoplasms - therapy Cancer Chitosan Chitosan - chemistry DNA - chemistry DNAzyme General pharmacology Humans Medical sciences Mice Mice, Inbred BALB C Mice, Nude Nanoparticle Nanoparticles - therapeutic use Osteosarcoma - therapy Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Tumour |
title | A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site |
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