RNA Interference Using c-Myc-Conjugated Nanoparticles Suppresses Breast and Colorectal Cancer Models.
Identifieur interne : 002D35 ( PubMed/Curation ); précédent : 002D34; suivant : 002D36RNA Interference Using c-Myc-Conjugated Nanoparticles Suppresses Breast and Colorectal Cancer Models.
Auteurs : Naveen K. Tangudu [Inde] ; Vinod K. Verma [Inde] ; Tristan D. Clemons [Australie] ; Syed S. Beevi [Inde] ; Trevor Hay [Royaume-Uni] ; Ganesh Mahidhara [Inde] ; Meera Raja [Royaume-Uni] ; Rekha A. Nair [Inde] ; Liza E. Alexander [Inde] ; Anant B. Patel [Inde] ; Jedy Jose [Inde] ; Nicole M. Smith [France] ; Bogdan Zdyrko [États-Unis] ; Anne Bourdoncle [France] ; Igor Luzinov [États-Unis] ; K Swaminathan Iyer [Australie] ; Alan R. Clarke [Royaume-Uni] ; Lekha Dinesh Kumar [Inde]Source :
- Molecular cancer therapeutics [ 1538-8514 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Cellules HEK293, Cellules Jurkat, Cellules MCF-7, Cellules NIH 3T3, Extinction de l'expression des gènes, Femelle, Humains, Interférence par ARN, Lignée cellulaire tumorale, Nanoconjugués, Oligonucléotides antisens (administration et posologie), Polypropylènes (), Protéines proto-oncogènes c-myc (antagonistes et inhibiteurs), Souris, Thérapie par l'interférence par ARN (), Transplantation tumorale, Tumeurs colorectales (), Tumeurs colorectales (génétique), Tumeurs du sein (), Tumeurs du sein (génétique).
- MESH :
- administration et posologie : Oligonucléotides antisens.
- antagonistes et inhibiteurs : Protéines proto-oncogènes c-myc.
- génétique : Tumeurs colorectales, Tumeurs du sein.
- Animaux, Cellules HEK293, Cellules Jurkat, Cellules MCF-7, Cellules NIH 3T3, Extinction de l'expression des gènes, Femelle, Humains, Interférence par ARN, Lignée cellulaire tumorale, Nanoconjugués, Polypropylènes, Souris, Thérapie par l'interférence par ARN, Transplantation tumorale, Tumeurs colorectales, Tumeurs du sein.
English descriptors
- KwdEn :
- Animals, Breast Neoplasms (genetics), Breast Neoplasms (therapy), Cell Line, Tumor, Colorectal Neoplasms (genetics), Colorectal Neoplasms (therapy), Female, Gene Silencing, HEK293 Cells, Humans, Jurkat Cells, MCF-7 Cells, Mice, NIH 3T3 Cells, Nanoconjugates, Neoplasm Transplantation, Oligonucleotides, Antisense (administration & dosage), Polypropylenes (chemistry), Proto-Oncogene Proteins c-myc (antagonists & inhibitors), RNA Interference, RNAi Therapeutics (methods).
- MESH :
- chemical , administration & dosage : Oligonucleotides, Antisense.
- chemical , antagonists & inhibitors : Proto-Oncogene Proteins c-myc.
- chemical , chemistry : Polypropylenes.
- chemical : Nanoconjugates.
- genetics : Breast Neoplasms, Colorectal Neoplasms.
- methods : RNAi Therapeutics.
- therapy : Breast Neoplasms, Colorectal Neoplasms.
- Animals, Cell Line, Tumor, Female, Gene Silencing, HEK293 Cells, Humans, Jurkat Cells, MCF-7 Cells, Mice, NIH 3T3 Cells, Neoplasm Transplantation, RNA Interference.
Abstract
In this article, we report the development and preclinical validation of combinatorial therapy for treatment of cancers using RNA interference (RNAi). RNAi technology is an attractive approach to silence genes responsible for disease onset and progression. Currently, the critical challenge facing the clinical success of RNAi technology is in the difficulty of delivery of RNAi inducers, due to low transfection efficiency, difficulties of integration into host DNA and unstable expression. Using the macromolecule polyglycidal methacrylate (PGMA) as a platform to graft multiple polyethyleneimine (PEI) chains, we demonstrate effective delivery of small oligos (anti-miRs and mimics) and larger DNAs (encoding shRNAs) in a wide variety of cancer cell lines by successful silencing/activation of their respective target genes. Furthermore, the effectiveness of this therapy was validated for in vivo tumor suppression using two transgenic mouse models; first, tumor growth arrest and increased animal survival was seen in mice bearing Brca2/p53-mutant mammary tumors following daily intratumoral treatment with nanoparticles conjugated to c-Myc shRNA. Second, oral delivery of the conjugate to an Apc-deficient crypt progenitor colon cancer model increased animal survival and returned intestinal tissue to a non-wnt-deregulated state. This study demonstrates, through careful design of nonviral nanoparticles and appropriate selection of therapeutic gene targets, that RNAi technology can be made an affordable and amenable therapy for cancer.
DOI: 10.1158/1535-7163.MCT-14-0970
PubMed: 25695957
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Smith</name><affiliation wicri:level="1"><nlm:affiliation>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac</wicri:regionArea></affiliation></author><author><name sortKey="Zdyrko, Bogdan" sort="Zdyrko, Bogdan" uniqKey="Zdyrko B" first="Bogdan" last="Zdyrko">Bogdan Zdyrko</name><affiliation wicri:level="2"><nlm:affiliation>School of Materials Science and Engineering, Clemson University, Clemson, South Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Sud</region></placeName><wicri:cityArea>School of Materials Science and Engineering, Clemson University, Clemson</wicri:cityArea></affiliation></author><author><name sortKey="Bourdoncle, Anne" sort="Bourdoncle, Anne" uniqKey="Bourdoncle A" first="Anne" last="Bourdoncle">Anne Bourdoncle</name><affiliation wicri:level="1"><nlm:affiliation>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac</wicri:regionArea></affiliation></author><author><name sortKey="Luzinov, Igor" sort="Luzinov, Igor" uniqKey="Luzinov I" first="Igor" last="Luzinov">Igor Luzinov</name><affiliation wicri:level="2"><nlm:affiliation>School of Materials Science and Engineering, Clemson University, Clemson, South Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Sud</region></placeName><wicri:cityArea>School of Materials Science and Engineering, Clemson University, Clemson</wicri:cityArea></affiliation></author><author><name sortKey="Iyer, K Swaminathan" sort="Iyer, K Swaminathan" uniqKey="Iyer K" first="K Swaminathan" last="Iyer">K Swaminathan Iyer</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Australia. lekha@ccmb.res.in swaminatha.iyer@uwa.edu.au ClarkeAR@cf.ac.uk.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry and Biochemistry, The University of Western Australia, Crawley</wicri:regionArea></affiliation></author><author><name sortKey="Clarke, Alan R" sort="Clarke, Alan R" uniqKey="Clarke A" first="Alan R" last="Clarke">Alan R. Clarke</name><affiliation wicri:level="1"><nlm:affiliation>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, United Kingdom. lekha@ccmb.res.in swaminatha.iyer@uwa.edu.au ClarkeAR@cf.ac.uk.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Dinesh Kumar, Lekha" sort="Dinesh Kumar, Lekha" uniqKey="Dinesh Kumar L" first="Lekha" last="Dinesh Kumar">Lekha Dinesh Kumar</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India. lekha@ccmb.res.in swaminatha.iyer@uwa.edu.au ClarkeAR@cf.ac.uk.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25695957</idno><idno type="pmid">25695957</idno><idno type="doi">10.1158/1535-7163.MCT-14-0970</idno><idno type="wicri:Area/PubMed/Corpus">002E11</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002E11</idno><idno type="wicri:Area/PubMed/Curation">002D35</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002D35</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">RNA Interference Using c-Myc-Conjugated Nanoparticles Suppresses Breast and Colorectal Cancer Models.</title><author><name sortKey="Tangudu, Naveen K" sort="Tangudu, Naveen K" uniqKey="Tangudu N" first="Naveen K" last="Tangudu">Naveen K. Tangudu</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad</wicri:regionArea></affiliation></author><author><name sortKey="Verma, Vinod K" sort="Verma, Vinod K" uniqKey="Verma V" first="Vinod K" last="Verma">Vinod K. Verma</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad</wicri:regionArea></affiliation></author><author><name sortKey="Clemons, Tristan D" sort="Clemons, Tristan D" uniqKey="Clemons T" first="Tristan D" last="Clemons">Tristan D. Clemons</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry and Biochemistry, The University of Western Australia, Crawley</wicri:regionArea></affiliation></author><author><name sortKey="Beevi, Syed S" sort="Beevi, Syed S" uniqKey="Beevi S" first="Syed S" last="Beevi">Syed S. Beevi</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad</wicri:regionArea></affiliation></author><author><name sortKey="Hay, Trevor" sort="Hay, Trevor" uniqKey="Hay T" first="Trevor" last="Hay">Trevor Hay</name><affiliation wicri:level="1"><nlm:affiliation>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Mahidhara, Ganesh" sort="Mahidhara, Ganesh" uniqKey="Mahidhara G" first="Ganesh" last="Mahidhara">Ganesh Mahidhara</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad</wicri:regionArea></affiliation></author><author><name sortKey="Raja, Meera" sort="Raja, Meera" uniqKey="Raja M" first="Meera" last="Raja">Meera Raja</name><affiliation wicri:level="1"><nlm:affiliation>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Nair, Rekha A" sort="Nair, Rekha A" uniqKey="Nair R" first="Rekha A" last="Nair">Rekha A. Nair</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, Regional Cancer Centre, Trivandrum, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Pathology, Regional Cancer Centre, Trivandrum</wicri:regionArea></affiliation></author><author><name sortKey="Alexander, Liza E" sort="Alexander, Liza E" uniqKey="Alexander L" first="Liza E" last="Alexander">Liza E. Alexander</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, Regional Cancer Centre, Trivandrum, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Pathology, Regional Cancer Centre, Trivandrum</wicri:regionArea></affiliation></author><author><name sortKey="Patel, Anant B" sort="Patel, Anant B" uniqKey="Patel A" first="Anant B" last="Patel">Anant B. Patel</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad</wicri:regionArea></affiliation></author><author><name sortKey="Jose, Jedy" sort="Jose, Jedy" uniqKey="Jose J" first="Jedy" last="Jose">Jedy Jose</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad</wicri:regionArea></affiliation></author><author><name sortKey="Smith, Nicole M" sort="Smith, Nicole M" uniqKey="Smith N" first="Nicole M" last="Smith">Nicole M. Smith</name><affiliation wicri:level="1"><nlm:affiliation>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac</wicri:regionArea></affiliation></author><author><name sortKey="Zdyrko, Bogdan" sort="Zdyrko, Bogdan" uniqKey="Zdyrko B" first="Bogdan" last="Zdyrko">Bogdan Zdyrko</name><affiliation wicri:level="2"><nlm:affiliation>School of Materials Science and Engineering, Clemson University, Clemson, South Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Sud</region></placeName><wicri:cityArea>School of Materials Science and Engineering, Clemson University, Clemson</wicri:cityArea></affiliation></author><author><name sortKey="Bourdoncle, Anne" sort="Bourdoncle, Anne" uniqKey="Bourdoncle A" first="Anne" last="Bourdoncle">Anne Bourdoncle</name><affiliation wicri:level="1"><nlm:affiliation>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac</wicri:regionArea></affiliation></author><author><name sortKey="Luzinov, Igor" sort="Luzinov, Igor" uniqKey="Luzinov I" first="Igor" last="Luzinov">Igor Luzinov</name><affiliation wicri:level="2"><nlm:affiliation>School of Materials Science and Engineering, Clemson University, Clemson, South Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Sud</region></placeName><wicri:cityArea>School of Materials Science and Engineering, Clemson University, Clemson</wicri:cityArea></affiliation></author><author><name sortKey="Iyer, K Swaminathan" sort="Iyer, K Swaminathan" uniqKey="Iyer K" first="K Swaminathan" last="Iyer">K Swaminathan Iyer</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Australia. lekha@ccmb.res.in swaminatha.iyer@uwa.edu.au ClarkeAR@cf.ac.uk.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry and Biochemistry, The University of Western Australia, Crawley</wicri:regionArea></affiliation></author><author><name sortKey="Clarke, Alan R" sort="Clarke, Alan R" uniqKey="Clarke A" first="Alan R" last="Clarke">Alan R. Clarke</name><affiliation wicri:level="1"><nlm:affiliation>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, United Kingdom. lekha@ccmb.res.in swaminatha.iyer@uwa.edu.au ClarkeAR@cf.ac.uk.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Dinesh Kumar, Lekha" sort="Dinesh Kumar, Lekha" uniqKey="Dinesh Kumar L" first="Lekha" last="Dinesh Kumar">Lekha Dinesh Kumar</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India. lekha@ccmb.res.in swaminatha.iyer@uwa.edu.au ClarkeAR@cf.ac.uk.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad</wicri:regionArea></affiliation></author></analytic><series><title level="j">Molecular cancer therapeutics</title><idno type="eISSN">1538-8514</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Breast Neoplasms (genetics)</term><term>Breast Neoplasms (therapy)</term><term>Cell Line, Tumor</term><term>Colorectal Neoplasms (genetics)</term><term>Colorectal Neoplasms (therapy)</term><term>Female</term><term>Gene Silencing</term><term>HEK293 Cells</term><term>Humans</term><term>Jurkat Cells</term><term>MCF-7 Cells</term><term>Mice</term><term>NIH 3T3 Cells</term><term>Nanoconjugates</term><term>Neoplasm Transplantation</term><term>Oligonucleotides, Antisense (administration & dosage)</term><term>Polypropylenes (chemistry)</term><term>Proto-Oncogene Proteins c-myc (antagonists & inhibitors)</term><term>RNA Interference</term><term>RNAi Therapeutics (methods)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Cellules Jurkat</term><term>Cellules MCF-7</term><term>Cellules NIH 3T3</term><term>Extinction de l'expression des gènes</term><term>Femelle</term><term>Humains</term><term>Interférence par ARN</term><term>Lignée cellulaire tumorale</term><term>Nanoconjugués</term><term>Oligonucléotides antisens (administration et posologie)</term><term>Polypropylènes ()</term><term>Protéines proto-oncogènes c-myc (antagonistes et inhibiteurs)</term><term>Souris</term><term>Thérapie par l'interférence par ARN ()</term><term>Transplantation tumorale</term><term>Tumeurs colorectales ()</term><term>Tumeurs colorectales (génétique)</term><term>Tumeurs du sein ()</term><term>Tumeurs du sein (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Oligonucleotides, Antisense</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Proto-Oncogene Proteins c-myc</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Polypropylenes</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Nanoconjugates</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Oligonucléotides antisens</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines proto-oncogènes c-myc</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Breast Neoplasms</term><term>Colorectal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Tumeurs colorectales</term><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>RNAi Therapeutics</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Breast Neoplasms</term><term>Colorectal Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Female</term><term>Gene Silencing</term><term>HEK293 Cells</term><term>Humans</term><term>Jurkat Cells</term><term>MCF-7 Cells</term><term>Mice</term><term>NIH 3T3 Cells</term><term>Neoplasm Transplantation</term><term>RNA Interference</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Cellules Jurkat</term><term>Cellules MCF-7</term><term>Cellules NIH 3T3</term><term>Extinction de l'expression des gènes</term><term>Femelle</term><term>Humains</term><term>Interférence par ARN</term><term>Lignée cellulaire tumorale</term><term>Nanoconjugués</term><term>Polypropylènes</term><term>Souris</term><term>Thérapie par l'interférence par ARN</term><term>Transplantation tumorale</term><term>Tumeurs colorectales</term><term>Tumeurs du sein</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In this article, we report the development and preclinical validation of combinatorial therapy for treatment of cancers using RNA interference (RNAi). RNAi technology is an attractive approach to silence genes responsible for disease onset and progression. Currently, the critical challenge facing the clinical success of RNAi technology is in the difficulty of delivery of RNAi inducers, due to low transfection efficiency, difficulties of integration into host DNA and unstable expression. Using the macromolecule polyglycidal methacrylate (PGMA) as a platform to graft multiple polyethyleneimine (PEI) chains, we demonstrate effective delivery of small oligos (anti-miRs and mimics) and larger DNAs (encoding shRNAs) in a wide variety of cancer cell lines by successful silencing/activation of their respective target genes. Furthermore, the effectiveness of this therapy was validated for in vivo tumor suppression using two transgenic mouse models; first, tumor growth arrest and increased animal survival was seen in mice bearing Brca2/p53-mutant mammary tumors following daily intratumoral treatment with nanoparticles conjugated to c-Myc shRNA. Second, oral delivery of the conjugate to an Apc-deficient crypt progenitor colon cancer model increased animal survival and returned intestinal tissue to a non-wnt-deregulated state. This study demonstrates, through careful design of nonviral nanoparticles and appropriate selection of therapeutic gene targets, that RNAi technology can be made an affordable and amenable therapy for cancer.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25695957</PMID><DateCreated><Year>2015</Year><Month>05</Month><Day>07</Day></DateCreated><DateCompleted><Year>2016</Year><Month>02</Month><Day>01</Day></DateCompleted><DateRevised><Year>2015</Year><Month>05</Month><Day>07</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1538-8514</ISSN><JournalIssue CitedMedium="Internet"><Volume>14</Volume><Issue>5</Issue><PubDate><Year>2015</Year><Month>May</Month></PubDate></JournalIssue><Title>Molecular cancer therapeutics</Title><ISOAbbreviation>Mol. Cancer Ther.</ISOAbbreviation></Journal><ArticleTitle>RNA Interference Using c-Myc-Conjugated Nanoparticles Suppresses Breast and Colorectal Cancer Models.</ArticleTitle><Pagination><MedlinePgn>1259-69</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1158/1535-7163.MCT-14-0970</ELocationID><Abstract><AbstractText>In this article, we report the development and preclinical validation of combinatorial therapy for treatment of cancers using RNA interference (RNAi). RNAi technology is an attractive approach to silence genes responsible for disease onset and progression. Currently, the critical challenge facing the clinical success of RNAi technology is in the difficulty of delivery of RNAi inducers, due to low transfection efficiency, difficulties of integration into host DNA and unstable expression. Using the macromolecule polyglycidal methacrylate (PGMA) as a platform to graft multiple polyethyleneimine (PEI) chains, we demonstrate effective delivery of small oligos (anti-miRs and mimics) and larger DNAs (encoding shRNAs) in a wide variety of cancer cell lines by successful silencing/activation of their respective target genes. Furthermore, the effectiveness of this therapy was validated for in vivo tumor suppression using two transgenic mouse models; first, tumor growth arrest and increased animal survival was seen in mice bearing Brca2/p53-mutant mammary tumors following daily intratumoral treatment with nanoparticles conjugated to c-Myc shRNA. Second, oral delivery of the conjugate to an Apc-deficient crypt progenitor colon cancer model increased animal survival and returned intestinal tissue to a non-wnt-deregulated state. This study demonstrates, through careful design of nonviral nanoparticles and appropriate selection of therapeutic gene targets, that RNAi technology can be made an affordable and amenable therapy for cancer.</AbstractText><CopyrightInformation>©2015 American Association for Cancer Research.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tangudu</LastName><ForeName>Naveen K</ForeName><Initials>NK</Initials><AffiliationInfo><Affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Verma</LastName><ForeName>Vinod K</ForeName><Initials>VK</Initials><AffiliationInfo><Affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Clemons</LastName><ForeName>Tristan D</ForeName><Initials>TD</Initials><AffiliationInfo><Affiliation>School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beevi</LastName><ForeName>Syed S</ForeName><Initials>SS</Initials><AffiliationInfo><Affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hay</LastName><ForeName>Trevor</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mahidhara</LastName><ForeName>Ganesh</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Raja</LastName><ForeName>Meera</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nair</LastName><ForeName>Rekha A</ForeName><Initials>RA</Initials><AffiliationInfo><Affiliation>Department of Pathology, Regional Cancer Centre, Trivandrum, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alexander</LastName><ForeName>Liza E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>Department of Pathology, Regional Cancer Centre, Trivandrum, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Patel</LastName><ForeName>Anant B</ForeName><Initials>AB</Initials><AffiliationInfo><Affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jose</LastName><ForeName>Jedy</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smith</LastName><ForeName>Nicole M</ForeName><Initials>NM</Initials><AffiliationInfo><Affiliation>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zdyrko</LastName><ForeName>Bogdan</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>School of Materials Science and Engineering, Clemson University, Clemson, South Carolina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bourdoncle</LastName><ForeName>Anne</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Univ de Bordeaux, INSERM U869, IECB, ARNA Laboratory, Pessac, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luzinov</LastName><ForeName>Igor</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>School of Materials Science and Engineering, Clemson University, Clemson, South Carolina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Iyer</LastName><ForeName>K Swaminathan</ForeName><Initials>KS</Initials><AffiliationInfo><Affiliation>School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Australia. lekha@ccmb.res.in swaminatha.iyer@uwa.edu.au ClarkeAR@cf.ac.uk.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Clarke</LastName><ForeName>Alan R</ForeName><Initials>AR</Initials><AffiliationInfo><Affiliation>European Cancer Stem Cell Research Institute, Cardiff University, Cathays, Cardiff, United Kingdom. lekha@ccmb.res.in swaminatha.iyer@uwa.edu.au ClarkeAR@cf.ac.uk.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dinesh Kumar</LastName><ForeName>Lekha</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Cancer Biology, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India. lekha@ccmb.res.in swaminatha.iyer@uwa.edu.au ClarkeAR@cf.ac.uk.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>02</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mol Cancer Ther</MedlineTA><NlmUniqueID>101132535</NlmUniqueID><ISSNLinking>1535-7163</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D058726">Nanoconjugates</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016376">Oligonucleotides, Antisense</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011126">Polypropylenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016271">Proto-Oncogene Proteins c-myc</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C443641">poly(propyleneimine)</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001943" MajorTopicYN="N">Breast Neoplasms</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015179" MajorTopicYN="N">Colorectal Neoplasms</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020868" MajorTopicYN="N">Gene Silencing</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019169" MajorTopicYN="N">Jurkat Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D061986" MajorTopicYN="N">MCF-7 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D041681" MajorTopicYN="N">NIH 3T3 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058726" MajorTopicYN="N">Nanoconjugates</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009368" MajorTopicYN="N">Neoplasm Transplantation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016376" MajorTopicYN="N">Oligonucleotides, Antisense</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011126" MajorTopicYN="N">Polypropylenes</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016271" MajorTopicYN="N">Proto-Oncogene Proteins c-myc</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D034622" MajorTopicYN="N">RNA Interference</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000067492" MajorTopicYN="N">RNAi Therapeutics</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>11</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>02</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>2</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>2</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>2</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25695957</ArticleId><ArticleId IdType="pii">1535-7163.MCT-14-0970</ArticleId><ArticleId IdType="doi">10.1158/1535-7163.MCT-14-0970</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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