Polymeric chloroquine as an inhibitor of cancer cell migration and experimental lung metastasis.
Identifieur interne : 000D59 ( Main/Exploration ); précédent : 000D58; suivant : 000D60Polymeric chloroquine as an inhibitor of cancer cell migration and experimental lung metastasis.
Auteurs : Fei Yu [États-Unis] ; Jing Li [États-Unis] ; Ying Xie [États-Unis] ; Richard L. Sleightholm [États-Unis] ; David Oupick [République populaire de Chine]Source :
- Journal of controlled release : official journal of the Controlled Release Society [ 1873-4995 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Antinéoplasiques (), Antinéoplasiques (administration et posologie), Antinéoplasiques (usage thérapeutique), Autophagie (), Chimiokine CXCL12 (pharmacologie), Chloroquine (), Chloroquine (administration et posologie), Chloroquine (usage thérapeutique), Extracellular Signal-Regulated MAP Kinases (métabolisme), Femelle, Humains, Lignée cellulaire tumorale, Mouvement cellulaire (), Polymères (), Polymères (administration et posologie), Récepteurs CXCR4 (antagonistes et inhibiteurs), Récepteurs CXCR4 (métabolisme), Souris de lignée BALB C, Survie cellulaire (), Systèmes de délivrance de médicaments, Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (traitement médicamenteux).
- MESH :
- administration et posologie : Antinéoplasiques, Chloroquine, Polymères.
- anatomopathologie : Tumeurs du poumon.
- antagonistes et inhibiteurs : Récepteurs CXCR4.
- métabolisme : Extracellular Signal-Regulated MAP Kinases, Récepteurs CXCR4.
- pharmacologie : Chimiokine CXCL12.
- traitement médicamenteux : Tumeurs du poumon.
- usage thérapeutique : Antinéoplasiques, Chloroquine.
- Animaux, Antinéoplasiques, Autophagie, Chloroquine, Femelle, Humains, Lignée cellulaire tumorale, Mouvement cellulaire, Polymères, Souris de lignée BALB C, Survie cellulaire, Systèmes de délivrance de médicaments.
English descriptors
- KwdEn :
- Animals, Antineoplastic Agents (administration & dosage), Antineoplastic Agents (chemistry), Antineoplastic Agents (therapeutic use), Autophagy (drug effects), Cell Line, Tumor, Cell Movement (drug effects), Cell Survival (drug effects), Chemokine CXCL12 (pharmacology), Chloroquine (administration & dosage), Chloroquine (chemistry), Chloroquine (therapeutic use), Drug Delivery Systems, Extracellular Signal-Regulated MAP Kinases (metabolism), Female, Humans, Lung Neoplasms (drug therapy), Lung Neoplasms (pathology), Mice, Inbred BALB C, Polymers (administration & dosage), Polymers (chemistry), Receptors, CXCR4 (antagonists & inhibitors), Receptors, CXCR4 (metabolism).
- MESH :
- chemical , administration & dosage : Antineoplastic Agents, Chloroquine, Polymers.
- chemical , antagonists & inhibitors : Receptors, CXCR4.
- chemical , chemistry : Antineoplastic Agents, Chloroquine, Polymers.
- chemical , metabolism : Extracellular Signal-Regulated MAP Kinases, Receptors, CXCR4.
- chemical , pharmacology : Chemokine CXCL12.
- chemical , therapeutic use : Antineoplastic Agents, Chloroquine.
- drug effects : Autophagy, Cell Movement, Cell Survival.
- drug therapy : Lung Neoplasms.
- pathology : Lung Neoplasms.
- Animals, Cell Line, Tumor, Drug Delivery Systems, Female, Humans, Mice, Inbred BALB C.
Abstract
Chloroquine (CQ) is a widely used antimalarial drug with emerging potential in anticancer therapies due to its apparent inhibitory effects on CXCR4 chemokine receptor, autophagy, and cholesterol metabolism. This study reports on polymeric CQ (pCQ) as a macromolecular drug with antimetastatic activity. The pCQ polymers were synthesized by copolymerization of methacryloylated hydroxy-CQ (HCQ) and N-(2-hydroxypropyl)methacrylamide (HPMA). The results show that pCQ is significantly more effective in inhibiting cancer cell migration and invasion when compared with the parent HCQ. The proposed mechanism of action at least partially relies on the ability of pCQ to inhibit cell migration mediated by the CXCR4/CXCL12 pathway. The pCQ also demonstrates superior inhibitory activity over HCQ when tested in a mouse model of experimental lung metastasis. Lastly, pCQ shows the ability to efficiently translocate to the cytoplasm while exhibiting lower cytotoxicity than HCQ. Overall, this study supports pCQ as a promising polymeric drug platform suitable for use in combination antimetastatic strategies and potential use in cytoplasmic drug delivery.
DOI: 10.1016/j.jconrel.2016.07.040
PubMed: 27473763
Affiliations:
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Sleightholm</name><affiliation wicri:level="2"><nlm:affiliation>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE</wicri:regionArea><placeName><region type="state">Nebraska</region></placeName></affiliation></author><author><name sortKey="Oupick, David" sort="Oupick, David" uniqKey="Oupick D" first="David" last="Oupick">David Oupick</name><affiliation wicri:level="1"><nlm:affiliation>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, China. Electronic address: david.oupicky@unmc.edu.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing</wicri:regionArea><wicri:noRegion>Nanjing</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of controlled release : official journal of the Controlled Release Society</title><idno type="eISSN">1873-4995</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antineoplastic Agents (administration & dosage)</term><term>Antineoplastic Agents (chemistry)</term><term>Antineoplastic Agents (therapeutic use)</term><term>Autophagy (drug effects)</term><term>Cell Line, Tumor</term><term>Cell Movement (drug effects)</term><term>Cell Survival (drug effects)</term><term>Chemokine CXCL12 (pharmacology)</term><term>Chloroquine (administration & dosage)</term><term>Chloroquine (chemistry)</term><term>Chloroquine (therapeutic use)</term><term>Drug Delivery Systems</term><term>Extracellular Signal-Regulated MAP Kinases (metabolism)</term><term>Female</term><term>Humans</term><term>Lung Neoplasms (drug therapy)</term><term>Lung Neoplasms (pathology)</term><term>Mice, Inbred BALB C</term><term>Polymers (administration & dosage)</term><term>Polymers (chemistry)</term><term>Receptors, CXCR4 (antagonists & inhibitors)</term><term>Receptors, CXCR4 (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antinéoplasiques ()</term><term>Antinéoplasiques (administration et posologie)</term><term>Antinéoplasiques (usage thérapeutique)</term><term>Autophagie ()</term><term>Chimiokine CXCL12 (pharmacologie)</term><term>Chloroquine ()</term><term>Chloroquine (administration et posologie)</term><term>Chloroquine (usage thérapeutique)</term><term>Extracellular Signal-Regulated MAP Kinases (métabolisme)</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Mouvement cellulaire ()</term><term>Polymères ()</term><term>Polymères (administration et posologie)</term><term>Récepteurs CXCR4 (antagonistes et inhibiteurs)</term><term>Récepteurs CXCR4 (métabolisme)</term><term>Souris de lignée BALB C</term><term>Survie cellulaire ()</term><term>Systèmes de délivrance de médicaments</term><term>Tumeurs du poumon (anatomopathologie)</term><term>Tumeurs du poumon (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antineoplastic Agents</term><term>Chloroquine</term><term>Polymers</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Receptors, CXCR4</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antineoplastic Agents</term><term>Chloroquine</term><term>Polymers</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Extracellular Signal-Regulated MAP Kinases</term><term>Receptors, CXCR4</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Chemokine CXCL12</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Agents</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Antinéoplasiques</term><term>Chloroquine</term><term>Polymères</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Récepteurs CXCR4</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term><term>Cell Movement</term><term>Cell Survival</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Extracellular Signal-Regulated MAP Kinases</term><term>Récepteurs CXCR4</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Chimiokine CXCL12</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antinéoplasiques</term><term>Chloroquine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Drug Delivery Systems</term><term>Female</term><term>Humans</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Antinéoplasiques</term><term>Autophagie</term><term>Chloroquine</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Mouvement cellulaire</term><term>Polymères</term><term>Souris de lignée BALB C</term><term>Survie cellulaire</term><term>Systèmes de délivrance de médicaments</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Chloroquine (CQ) is a widely used antimalarial drug with emerging potential in anticancer therapies due to its apparent inhibitory effects on CXCR4 chemokine receptor, autophagy, and cholesterol metabolism. This study reports on polymeric CQ (pCQ) as a macromolecular drug with antimetastatic activity. The pCQ polymers were synthesized by copolymerization of methacryloylated hydroxy-CQ (HCQ) and N-(2-hydroxypropyl)methacrylamide (HPMA). The results show that pCQ is significantly more effective in inhibiting cancer cell migration and invasion when compared with the parent HCQ. The proposed mechanism of action at least partially relies on the ability of pCQ to inhibit cell migration mediated by the CXCR4/CXCL12 pathway. The pCQ also demonstrates superior inhibitory activity over HCQ when tested in a mouse model of experimental lung metastasis. Lastly, pCQ shows the ability to efficiently translocate to the cytoplasm while exhibiting lower cytotoxicity than HCQ. Overall, this study supports pCQ as a promising polymeric drug platform suitable for use in combination antimetastatic strategies and potential use in cytoplasmic drug delivery.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Nebraska</li></region></list><tree><country name="États-Unis"><region name="Nebraska"><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name></region><name sortKey="Li, Jing" sort="Li, Jing" uniqKey="Li J" first="Jing" last="Li">Jing Li</name><name sortKey="Sleightholm, Richard L" sort="Sleightholm, Richard L" uniqKey="Sleightholm R" first="Richard L" last="Sleightholm">Richard L. Sleightholm</name><name sortKey="Xie, Ying" sort="Xie, Ying" uniqKey="Xie Y" first="Ying" last="Xie">Ying Xie</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Oupick, David" sort="Oupick, David" uniqKey="Oupick D" first="David" last="Oupick">David Oupick</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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