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Reversal of lung cancer multidrug resistance by pH-responsive micelleplexes mediating co-delivery of siRNA and paclitaxel.

Identifieur interne : 001007 ( Main/Exploration ); précédent : 001006; suivant : 001008

Reversal of lung cancer multidrug resistance by pH-responsive micelleplexes mediating co-delivery of siRNA and paclitaxel.

Auteurs : Haijun Yu [République populaire de Chine] ; Zhiai Xu ; Xianzhi Chen ; Leilei Xu ; Qi Yin ; Zhiwen Zhang ; Yaping Li

Source :

RBID : pubmed:23966347

Descripteurs français

English descriptors

Abstract

The recent advances in RNA interference (RNAi) technology provided novel and promising solutions for human cancer treatment. In this study, the application of dual pH-responsive cationic micellar nanoparticles for small interfering RNA (siRNA) and paclitaxel (PTX) co-delivery to overcome cancer multidrug resistance (MDR) is reported. The in vitro siRNA transfection shows that siRNA-luciferase (Luc) loaded micelleplexes efficiently silences Luc expression in various carcinoma cell lines. The Luc knockdown ability of the micelleplexes can be enhanced by choloquine (CQ) co-incubation. However, is abolished by bafilomycin-A1 (Baf-A1) treatment. The micelleplexes are further exploited for co-delivery of siRNA-Bcl-2 and PTX to Bcl-2 overexpressing A549 lung cancer cells (A549-Bcl-2). The experimental results show that the micelleplexes could sensitize A549-Bcl-2 cells to PTX via down-regulation of anti-apoptosis gene of Bcl-2, suggesting that PDMA-b-PDPA micelleplexes are promising nanovectors for siRNA and anti-cancer drug co-delivery to overcome cancer MDR.

DOI: 10.1002/mabi.201300282
PubMed: 23966347


Affiliations:


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Le document en format XML

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<name sortKey="Zhang, Zhiwen" sort="Zhang, Zhiwen" uniqKey="Zhang Z" first="Zhiwen" last="Zhang">Zhiwen Zhang</name>
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<term>Apoptosis (drug effects)</term>
<term>Apoptosis (genetics)</term>
<term>Cell Line, Tumor</term>
<term>Chloroquine (pharmacology)</term>
<term>Drug Carriers</term>
<term>Drug Resistance, Multiple (drug effects)</term>
<term>Drug Resistance, Multiple (genetics)</term>
<term>Drug Resistance, Neoplasm (drug effects)</term>
<term>Drug Resistance, Neoplasm (genetics)</term>
<term>Gene Knockdown Techniques</term>
<term>Humans</term>
<term>Hydrogen-Ion Concentration</term>
<term>Luciferases (genetics)</term>
<term>Lung Neoplasms (drug therapy)</term>
<term>Lung Neoplasms (genetics)</term>
<term>Lung Neoplasms (pathology)</term>
<term>Macrolides (pharmacology)</term>
<term>Micelles</term>
<term>Nanoparticles (administration & dosage)</term>
<term>Nanoparticles (chemistry)</term>
<term>Paclitaxel (administration & dosage)</term>
<term>Paclitaxel (pharmacology)</term>
<term>Polymethacrylic Acids</term>
<term>Proto-Oncogene Proteins c-bcl-2 (genetics)</term>
<term>RNA, Small Interfering (administration & dosage)</term>
<term>RNA, Small Interfering (genetics)</term>
<term>Transfection</term>
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<term>Antinéoplasiques d'origine végétale (administration et posologie)</term>
<term>Antinéoplasiques d'origine végétale (pharmacologie)</term>
<term>Apoptose ()</term>
<term>Apoptose (génétique)</term>
<term>Chloroquine (pharmacologie)</term>
<term>Concentration en ions d'hydrogène</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Luciferases (génétique)</term>
<term>Macrolides (pharmacologie)</term>
<term>Micelles</term>
<term>Multirésistance aux médicaments ()</term>
<term>Multirésistance aux médicaments (génétique)</term>
<term>Nanoparticules ()</term>
<term>Nanoparticules (administration et posologie)</term>
<term>Paclitaxel (administration et posologie)</term>
<term>Paclitaxel (pharmacologie)</term>
<term>Petit ARN interférent (administration et posologie)</term>
<term>Petit ARN interférent (génétique)</term>
<term>Poly(acides méthacryliques)</term>
<term>Protéines proto-oncogènes c-bcl-2 (génétique)</term>
<term>Résistance aux médicaments antinéoplasiques ()</term>
<term>Résistance aux médicaments antinéoplasiques (génétique)</term>
<term>Techniques de knock-down de gènes</term>
<term>Transfection</term>
<term>Tumeurs du poumon (anatomopathologie)</term>
<term>Tumeurs du poumon (génétique)</term>
<term>Tumeurs du poumon (traitement médicamenteux)</term>
<term>Vecteurs de médicaments</term>
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<term>Antineoplastic Agents, Phytogenic</term>
<term>Paclitaxel</term>
<term>RNA, Small Interfering</term>
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<term>Luciferases</term>
<term>Proto-Oncogene Proteins c-bcl-2</term>
<term>RNA, Small Interfering</term>
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<term>Chloroquine</term>
<term>Macrolides</term>
<term>Paclitaxel</term>
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<term>Paclitaxel</term>
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<term>Nanoparticles</term>
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<term>Protéines proto-oncogènes c-bcl-2</term>
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<term>Micelles</term>
<term>Multirésistance aux médicaments</term>
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<term>Résistance aux médicaments antinéoplasiques</term>
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<div type="abstract" xml:lang="en">The recent advances in RNA interference (RNAi) technology provided novel and promising solutions for human cancer treatment. In this study, the application of dual pH-responsive cationic micellar nanoparticles for small interfering RNA (siRNA) and paclitaxel (PTX) co-delivery to overcome cancer multidrug resistance (MDR) is reported. The in vitro siRNA transfection shows that siRNA-luciferase (Luc) loaded micelleplexes efficiently silences Luc expression in various carcinoma cell lines. The Luc knockdown ability of the micelleplexes can be enhanced by choloquine (CQ) co-incubation. However, is abolished by bafilomycin-A1 (Baf-A1) treatment. The micelleplexes are further exploited for co-delivery of siRNA-Bcl-2 and PTX to Bcl-2 overexpressing A549 lung cancer cells (A549-Bcl-2). The experimental results show that the micelleplexes could sensitize A549-Bcl-2 cells to PTX via down-regulation of anti-apoptosis gene of Bcl-2, suggesting that PDMA-b-PDPA micelleplexes are promising nanovectors for siRNA and anti-cancer drug co-delivery to overcome cancer MDR. </div>
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