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Co-delivery of paclitaxel and tetrandrine via iRGD peptide conjugated lipid-polymer hybrid nanoparticles overcome multidrug resistance in cancer cells
Zhang, Jinming1,2; Wang, Lu1; Chan, Hon Fai3; Xie, Wei4; Chen, Sheng4; He, Chengwei1; Wang, Yitao1; Chen, Meiwan1
2017-05-04
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume7
Abstract

One of the promising strategies to overcome tumor multidrug resistance (MDR) is to deliver anticancer drug along with P-glycoprotein (P-gp) inhibitor simultaneously. To enhance the cancer cellular internalization and implement the controlled drug release, herein an iRGD peptide-modified lipid-polymer hybrid nanosystem (LPN) was fabricated to coload paclitaxel (PTX) and tetrandrine (TET) at a precise combination ratio. In this co-delivery system, PTX was covalently conjugated to poly (D, L-lactide-co-glycolide) polymeric core by redox-sensitive disulfide bond, while TET was physically capsulated spontaneously for the aim to suppress P-gp in advance by the earlier released TET in cancer cells. As a result, the PTX+TET/iRGD LPNs with a core-shell structure possessed high drug loading efficiency, stability and redox-sensitive drug release profiles. Owing to the enhanced cellular uptake and P-gp suppression mediated by TET, significantly more PTX accumulated in A2780/PTX cells treated with PTX+TET/iRGD LPNs than either free drugs or non-iRGD modified LPNs. As expected, PTX+TET/iRGD LPNs presented the highest cytotoxicity against A2780/PTX cells and effectively promoted ROS production, enhanced apoptosis and cell cycle arrests particularly. Taken together, the co-delivery system demonstrated great promise as potential treatment for MDR-related tumors based on the synergistic effects of P-gp inhibition, enhanced endocytosis and intracellular sequentially drug release.

DOIhttp://doi.org/10.1038/srep46057
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000400554700001
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
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Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorChen, Meiwan
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
2.School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
3.Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
4.Department of Respiratory Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhang, Jinming,Wang, Lu,Chan, Hon Fai,et al. Co-delivery of paclitaxel and tetrandrine via iRGD peptide conjugated lipid-polymer hybrid nanoparticles overcome multidrug resistance in cancer cells[J]. SCIENTIFIC REPORTS,2017,7.
APA Zhang, Jinming.,Wang, Lu.,Chan, Hon Fai.,Xie, Wei.,Chen, Sheng.,...&Chen, Meiwan.(2017).Co-delivery of paclitaxel and tetrandrine via iRGD peptide conjugated lipid-polymer hybrid nanoparticles overcome multidrug resistance in cancer cells.SCIENTIFIC REPORTS,7.
MLA Zhang, Jinming,et al."Co-delivery of paclitaxel and tetrandrine via iRGD peptide conjugated lipid-polymer hybrid nanoparticles overcome multidrug resistance in cancer cells".SCIENTIFIC REPORTS 7(2017).
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