Chloroquine in combination with aptamer-modified nanocomplexes for tumor vessel normalization and efficient erlotinib/Survivin shRNA co-delivery to overcome drug resistance in EGFR-mutated non-small cell lung cancer.
Identifieur interne : 000C44 ( Main/Exploration ); précédent : 000C43; suivant : 000C45Chloroquine in combination with aptamer-modified nanocomplexes for tumor vessel normalization and efficient erlotinib/Survivin shRNA co-delivery to overcome drug resistance in EGFR-mutated non-small cell lung cancer.
Auteurs : Tingting Lv [République populaire de Chine] ; Ziying Li [République populaire de Chine] ; Liang Xu [République populaire de Chine] ; Yingying Zhang [République populaire de Chine] ; Haijun Chen [République populaire de Chine] ; Yu Gao [République populaire de Chine]Source :
- Acta biomaterialia [ 1878-7568 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Aptamères nucléotidiques (), Aptamères nucléotidiques (pharmacocinétique), Aptamères nucléotidiques (pharmacologie), Carcinome pulmonaire non à petites cellules (anatomopathologie), Carcinome pulmonaire non à petites cellules (génétique), Carcinome pulmonaire non à petites cellules (métabolisme), Carcinome pulmonaire non à petites cellules (traitement médicamenteux), Chlorhydrate d'erlotinib (), Chlorhydrate d'erlotinib (pharmacocinétique), Chlorhydrate d'erlotinib (pharmacologie), Chloroquine (), Chloroquine (pharmacocinétique), Chloroquine (pharmacologie), Femelle, Humains, Lignée cellulaire tumorale, Mutation, Nanoparticules (), Nanoparticules (usage thérapeutique), Petit ARN interférent (), Petit ARN interférent (pharmacocinétique), Petit ARN interférent (pharmacologie), Protéines tumorales (génétique), Protéines tumorales (métabolisme), Récepteurs ErbB (génétique), Récepteurs ErbB (métabolisme), Résistance aux médicaments antinéoplasiques (), Résistance aux médicaments antinéoplasiques (génétique), Souris, Souris de lignée BALB C, Souris nude, Tests d'activité antitumorale sur modèle de xénogreffe, Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (génétique), Tumeurs du poumon (métabolisme), Tumeurs du poumon (traitement médicamenteux).
- MESH :
- anatomopathologie : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- génétique : Carcinome pulmonaire non à petites cellules, Protéines tumorales, Récepteurs ErbB, Résistance aux médicaments antinéoplasiques, Tumeurs du poumon.
- métabolisme : Carcinome pulmonaire non à petites cellules, Protéines tumorales, Récepteurs ErbB, Tumeurs du poumon.
- pharmacocinétique : Aptamères nucléotidiques, Chlorhydrate d'erlotinib, Chloroquine, Petit ARN interférent.
- pharmacologie : Aptamères nucléotidiques, Chlorhydrate d'erlotinib, Chloroquine, Petit ARN interférent.
- traitement médicamenteux : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- usage thérapeutique : Nanoparticules.
- Animaux, Aptamères nucléotidiques, Chlorhydrate d'erlotinib, Chloroquine, Femelle, Humains, Lignée cellulaire tumorale, Mutation, Nanoparticules, Petit ARN interférent, Résistance aux médicaments antinéoplasiques, Souris, Souris de lignée BALB C, Souris nude, Tests d'activité antitumorale sur modèle de xénogreffe.
English descriptors
- KwdEn :
- Animals, Aptamers, Nucleotide (chemistry), Aptamers, Nucleotide (pharmacokinetics), Aptamers, Nucleotide (pharmacology), Carcinoma, Non-Small-Cell Lung (drug therapy), Carcinoma, Non-Small-Cell Lung (genetics), Carcinoma, Non-Small-Cell Lung (metabolism), Carcinoma, Non-Small-Cell Lung (pathology), Cell Line, Tumor, Chloroquine (chemistry), Chloroquine (pharmacokinetics), Chloroquine (pharmacology), Drug Resistance, Neoplasm (drug effects), Drug Resistance, Neoplasm (genetics), ErbB Receptors (genetics), ErbB Receptors (metabolism), Erlotinib Hydrochloride (chemistry), Erlotinib Hydrochloride (pharmacokinetics), Erlotinib Hydrochloride (pharmacology), Female, Humans, Lung Neoplasms (drug therapy), Lung Neoplasms (genetics), Lung Neoplasms (metabolism), Lung Neoplasms (pathology), Mice, Mice, Inbred BALB C, Mice, Nude, Mutation, Nanoparticles (chemistry), Nanoparticles (therapeutic use), Neoplasm Proteins (genetics), Neoplasm Proteins (metabolism), RNA, Small Interfering (chemistry), RNA, Small Interfering (pharmacokinetics), RNA, Small Interfering (pharmacology), Survivin, Xenograft Model Antitumor Assays.
- MESH :
- chemical , chemistry : Aptamers, Nucleotide, Chloroquine, Erlotinib Hydrochloride, RNA, Small Interfering.
- chemical , genetics : ErbB Receptors, Neoplasm Proteins.
- chemical , metabolism : ErbB Receptors, Neoplasm Proteins.
- chemical , pharmacokinetics : Aptamers, Nucleotide, Chloroquine, Erlotinib Hydrochloride, RNA, Small Interfering.
- chemical , pharmacology : Aptamers, Nucleotide, Chloroquine, Erlotinib Hydrochloride, RNA, Small Interfering.
- chemistry : Nanoparticles.
- drug effects : Drug Resistance, Neoplasm.
- drug therapy : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- genetics : Carcinoma, Non-Small-Cell Lung, Drug Resistance, Neoplasm, Lung Neoplasms.
- metabolism : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- pathology : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- therapeutic use : Nanoparticles.
- Animals, Cell Line, Tumor, Female, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Mutation, Survivin, Xenograft Model Antitumor Assays.
Abstract
Although novel molecular targeted drugs have been recognized as an effective therapy for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations, their efficacy fails to meet the expectation due to the acquired resistance in tumors. Up-regulation of the anti-apoptotic protein Survivin was shown to contribute to the resistance to EGFR tyrosine kinase inhibitors (TKI) in EGFR mutation-positive NSCLC. However, the unorganized tumor blood vessels impeded drug penetration into tumor tissue. The resulting insufficient intracellular drug/gene delivery in drug-resistant cancer cells remarkably weakened the drug efficacy in NSCLC. In this work, a multi-functional drug delivery system AP/ES was developed by using anti-EGFR aptamer (Apt)-modified polyamidoamine to co-deliver erlotinib and Survivin-shRNA. Chloroquine (CQ) was used in combination with AP/ES to normalize tumor vessels for sufficient drug/gene delivery to overcome drug resistance in NSCLC cells. The obtained AP/ES possessed desired physicochemical properties, good biostability, controlled drug release profiles, and strong selectivity to EGFR-mutated NSCLC mediated by Apt. CQ not only enhanced endosomal escape ability of AP/ES for efficient gene transfection to inhibit Survivin, but also showed strong vessel-normalization ability to improve tumor microcirculation, which further promoted drug delivery and enhanced drug efficacy in erlotinib-resistant NSCLC cells. Our innovative gene/drug co-delivery system in combination with CQ showed a promising outcome in fighting against erlotinib resistance both in vitro and in vivo. This work indicates that normalization of tumor vessels could help intracellular erlotinib/Survivin-shRNA delivery and the down-regulation of Survivin could act synergistically with erlotinib for reversal of erlotinib resistance in EGFR mutation-positive NSCLC.
DOI: 10.1016/j.actbio.2018.06.034
PubMed: 29960010
Affiliations:
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Le document en format XML
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<author><name sortKey="Gao, Yu" sort="Gao, Yu" uniqKey="Gao Y" first="Yu" last="Gao">Yu Gao</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Chloroquine in combination with aptamer-modified nanocomplexes for tumor vessel normalization and efficient erlotinib/Survivin shRNA co-delivery to overcome drug resistance in EGFR-mutated non-small cell lung cancer.</title>
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<author><name sortKey="Xu, Liang" sort="Xu, Liang" uniqKey="Xu L" first="Liang" last="Xu">Liang Xu</name>
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<author><name sortKey="Zhang, Yingying" sort="Zhang, Yingying" uniqKey="Zhang Y" first="Yingying" last="Zhang">Yingying Zhang</name>
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<author><name sortKey="Chen, Haijun" sort="Chen, Haijun" uniqKey="Chen H" first="Haijun" last="Chen">Haijun Chen</name>
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<author><name sortKey="Gao, Yu" sort="Gao, Yu" uniqKey="Gao Y" first="Yu" last="Gao">Yu Gao</name>
<affiliation wicri:level="1"><nlm:affiliation>Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian 350116, China. Electronic address: hellogaoyu@126.com.</nlm:affiliation>
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<series><title level="j">Acta biomaterialia</title>
<idno type="eISSN">1878-7568</idno>
<imprint><date when="2018" type="published">2018</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Aptamers, Nucleotide (chemistry)</term>
<term>Aptamers, Nucleotide (pharmacokinetics)</term>
<term>Aptamers, Nucleotide (pharmacology)</term>
<term>Carcinoma, Non-Small-Cell Lung (drug therapy)</term>
<term>Carcinoma, Non-Small-Cell Lung (genetics)</term>
<term>Carcinoma, Non-Small-Cell Lung (metabolism)</term>
<term>Carcinoma, Non-Small-Cell Lung (pathology)</term>
<term>Cell Line, Tumor</term>
<term>Chloroquine (chemistry)</term>
<term>Chloroquine (pharmacokinetics)</term>
<term>Chloroquine (pharmacology)</term>
<term>Drug Resistance, Neoplasm (drug effects)</term>
<term>Drug Resistance, Neoplasm (genetics)</term>
<term>ErbB Receptors (genetics)</term>
<term>ErbB Receptors (metabolism)</term>
<term>Erlotinib Hydrochloride (chemistry)</term>
<term>Erlotinib Hydrochloride (pharmacokinetics)</term>
<term>Erlotinib Hydrochloride (pharmacology)</term>
<term>Female</term>
<term>Humans</term>
<term>Lung Neoplasms (drug therapy)</term>
<term>Lung Neoplasms (genetics)</term>
<term>Lung Neoplasms (metabolism)</term>
<term>Lung Neoplasms (pathology)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Nude</term>
<term>Mutation</term>
<term>Nanoparticles (chemistry)</term>
<term>Nanoparticles (therapeutic use)</term>
<term>Neoplasm Proteins (genetics)</term>
<term>Neoplasm Proteins (metabolism)</term>
<term>RNA, Small Interfering (chemistry)</term>
<term>RNA, Small Interfering (pharmacokinetics)</term>
<term>RNA, Small Interfering (pharmacology)</term>
<term>Survivin</term>
<term>Xenograft Model Antitumor Assays</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Aptamères nucléotidiques ()</term>
<term>Aptamères nucléotidiques (pharmacocinétique)</term>
<term>Aptamères nucléotidiques (pharmacologie)</term>
<term>Carcinome pulmonaire non à petites cellules (anatomopathologie)</term>
<term>Carcinome pulmonaire non à petites cellules (génétique)</term>
<term>Carcinome pulmonaire non à petites cellules (métabolisme)</term>
<term>Carcinome pulmonaire non à petites cellules (traitement médicamenteux)</term>
<term>Chlorhydrate d'erlotinib ()</term>
<term>Chlorhydrate d'erlotinib (pharmacocinétique)</term>
<term>Chlorhydrate d'erlotinib (pharmacologie)</term>
<term>Chloroquine ()</term>
<term>Chloroquine (pharmacocinétique)</term>
<term>Chloroquine (pharmacologie)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Mutation</term>
<term>Nanoparticules ()</term>
<term>Nanoparticules (usage thérapeutique)</term>
<term>Petit ARN interférent ()</term>
<term>Petit ARN interférent (pharmacocinétique)</term>
<term>Petit ARN interférent (pharmacologie)</term>
<term>Protéines tumorales (génétique)</term>
<term>Protéines tumorales (métabolisme)</term>
<term>Récepteurs ErbB (génétique)</term>
<term>Récepteurs ErbB (métabolisme)</term>
<term>Résistance aux médicaments antinéoplasiques ()</term>
<term>Résistance aux médicaments antinéoplasiques (génétique)</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Souris nude</term>
<term>Tests d'activité antitumorale sur modèle de xénogreffe</term>
<term>Tumeurs du poumon (anatomopathologie)</term>
<term>Tumeurs du poumon (génétique)</term>
<term>Tumeurs du poumon (métabolisme)</term>
<term>Tumeurs du poumon (traitement médicamenteux)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Aptamers, Nucleotide</term>
<term>Chloroquine</term>
<term>Erlotinib Hydrochloride</term>
<term>RNA, Small Interfering</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>ErbB Receptors</term>
<term>Neoplasm Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>ErbB Receptors</term>
<term>Neoplasm Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Aptamers, Nucleotide</term>
<term>Chloroquine</term>
<term>Erlotinib Hydrochloride</term>
<term>RNA, Small Interfering</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Aptamers, Nucleotide</term>
<term>Chloroquine</term>
<term>Erlotinib Hydrochloride</term>
<term>RNA, Small Interfering</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Nanoparticles</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Drug Resistance, Neoplasm</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term>
<term>Drug Resistance, Neoplasm</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term>
<term>Protéines tumorales</term>
<term>Récepteurs ErbB</term>
<term>Résistance aux médicaments antinéoplasiques</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term>
<term>Protéines tumorales</term>
<term>Récepteurs ErbB</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Aptamères nucléotidiques</term>
<term>Chlorhydrate d'erlotinib</term>
<term>Chloroquine</term>
<term>Petit ARN interférent</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Aptamères nucléotidiques</term>
<term>Chlorhydrate d'erlotinib</term>
<term>Chloroquine</term>
<term>Petit ARN interférent</term>
</keywords>
<keywords scheme="MESH" qualifier="therapeutic use" xml:lang="en"><term>Nanoparticles</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Nanoparticules</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line, Tumor</term>
<term>Female</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Nude</term>
<term>Mutation</term>
<term>Survivin</term>
<term>Xenograft Model Antitumor Assays</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Aptamères nucléotidiques</term>
<term>Chlorhydrate d'erlotinib</term>
<term>Chloroquine</term>
<term>Femelle</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Mutation</term>
<term>Nanoparticules</term>
<term>Petit ARN interférent</term>
<term>Résistance aux médicaments antinéoplasiques</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Souris nude</term>
<term>Tests d'activité antitumorale sur modèle de xénogreffe</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en">Although novel molecular targeted drugs have been recognized as an effective therapy for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations, their efficacy fails to meet the expectation due to the acquired resistance in tumors. Up-regulation of the anti-apoptotic protein Survivin was shown to contribute to the resistance to EGFR tyrosine kinase inhibitors (TKI) in EGFR mutation-positive NSCLC. However, the unorganized tumor blood vessels impeded drug penetration into tumor tissue. The resulting insufficient intracellular drug/gene delivery in drug-resistant cancer cells remarkably weakened the drug efficacy in NSCLC. In this work, a multi-functional drug delivery system AP/ES was developed by using anti-EGFR aptamer (Apt)-modified polyamidoamine to co-deliver erlotinib and Survivin-shRNA. Chloroquine (CQ) was used in combination with AP/ES to normalize tumor vessels for sufficient drug/gene delivery to overcome drug resistance in NSCLC cells. The obtained AP/ES possessed desired physicochemical properties, good biostability, controlled drug release profiles, and strong selectivity to EGFR-mutated NSCLC mediated by Apt. CQ not only enhanced endosomal escape ability of AP/ES for efficient gene transfection to inhibit Survivin, but also showed strong vessel-normalization ability to improve tumor microcirculation, which further promoted drug delivery and enhanced drug efficacy in erlotinib-resistant NSCLC cells. Our innovative gene/drug co-delivery system in combination with CQ showed a promising outcome in fighting against erlotinib resistance both in vitro and in vivo. This work indicates that normalization of tumor vessels could help intracellular erlotinib/Survivin-shRNA delivery and the down-regulation of Survivin could act synergistically with erlotinib for reversal of erlotinib resistance in EGFR mutation-positive NSCLC.</div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Lv, Tingting" sort="Lv, Tingting" uniqKey="Lv T" first="Tingting" last="Lv">Tingting Lv</name>
</noRegion>
<name sortKey="Chen, Haijun" sort="Chen, Haijun" uniqKey="Chen H" first="Haijun" last="Chen">Haijun Chen</name>
<name sortKey="Gao, Yu" sort="Gao, Yu" uniqKey="Gao Y" first="Yu" last="Gao">Yu Gao</name>
<name sortKey="Li, Ziying" sort="Li, Ziying" uniqKey="Li Z" first="Ziying" last="Li">Ziying Li</name>
<name sortKey="Xu, Liang" sort="Xu, Liang" uniqKey="Xu L" first="Liang" last="Xu">Liang Xu</name>
<name sortKey="Zhang, Yingying" sort="Zhang, Yingying" uniqKey="Zhang Y" first="Yingying" last="Zhang">Yingying Zhang</name>
</country>
</tree>
</affiliations>
</record>
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