Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance

Xiwei Yu,1,* Guang Yang,2,* Yijie Shi,1 Chang Su,3 Ming Liu,1 Bo Feng,1 Liang Zhao1 1School of Pharmacy, Liaoning Medical University, Jinzhou, People’s Republic of China; 2Department of Oncology, BenQ Medical Center, Nanjing Medical University, Nanjing, People’s Republic of Chin...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Yu XW, Yang G, Shi YJ, Su C, Liu M, Feng B, Zhao L
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://doaj.org/article/a0b94ca4acc64a8f90f8c73593f00820
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:a0b94ca4acc64a8f90f8c73593f00820
record_format dspace
spelling oai:doaj.org-article:a0b94ca4acc64a8f90f8c73593f008202021-12-02T07:46:32ZIntracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance1178-2013https://doaj.org/article/a0b94ca4acc64a8f90f8c73593f008202015-11-01T00:00:00Zhttps://www.dovepress.com/intracellular-targeted-co-delivery-of-shmdr1-and-gefitinib-with-chitos-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiwei Yu,1,* Guang Yang,2,* Yijie Shi,1 Chang Su,3 Ming Liu,1 Bo Feng,1 Liang Zhao1 1School of Pharmacy, Liaoning Medical University, Jinzhou, People’s Republic of China; 2Department of Oncology, BenQ Medical Center, Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Veterinary Medicine, Liaoning Medical University, Jinzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Nowadays, multidrug resistance and side effects of drugs limit the effectiveness of chemotherapies in clinics. P-glycoprotein (P-gp) (MDR1), as a member of the ATP-binding cassette family, acts on transporting drugs into cell plasma across the membrane of cancer cells and leads to the occurrence of multidrug resistance, thus resulting in the failure of chemotherapy in cancer. The main aims of this research were to design a nanodelivery system for accomplishing the effective co-delivery of gene and antitumor drug and overcoming multidrug resistance effect. In this study, shMDR1 and gefitinib-encapsulating chitosan nanoparticles with sustained release, small particle size, and high encapsulation efficiency were prepared. The serum stability, protection from nuclease, and transfection efficiency of gene in vitro were investigated. The effects of co-delivery of shMDR1 and gefitinib in nanoparticles on reversing multidrug resistance were also evaluated by investigating the cytotoxicity, cellular uptake mechanism, and cell apoptosis on established gefitinib-resistant cells. The results demonstrated that chitosan nanoparticles entrapping gefitinib and shMDR1 had the potential to overcome the multidrug resistance and improve cancer treatment efficacy, especially toward resistant cells. Keywords: P-glycoprotein, nanodelivery system, chemotherapy, geneYu XWYang GShi YJSu CLiu MFeng BZhao LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 7045-7056 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Yu XW
Yang G
Shi YJ
Su C
Liu M
Feng B
Zhao L
Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance
description Xiwei Yu,1,* Guang Yang,2,* Yijie Shi,1 Chang Su,3 Ming Liu,1 Bo Feng,1 Liang Zhao1 1School of Pharmacy, Liaoning Medical University, Jinzhou, People’s Republic of China; 2Department of Oncology, BenQ Medical Center, Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Veterinary Medicine, Liaoning Medical University, Jinzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Nowadays, multidrug resistance and side effects of drugs limit the effectiveness of chemotherapies in clinics. P-glycoprotein (P-gp) (MDR1), as a member of the ATP-binding cassette family, acts on transporting drugs into cell plasma across the membrane of cancer cells and leads to the occurrence of multidrug resistance, thus resulting in the failure of chemotherapy in cancer. The main aims of this research were to design a nanodelivery system for accomplishing the effective co-delivery of gene and antitumor drug and overcoming multidrug resistance effect. In this study, shMDR1 and gefitinib-encapsulating chitosan nanoparticles with sustained release, small particle size, and high encapsulation efficiency were prepared. The serum stability, protection from nuclease, and transfection efficiency of gene in vitro were investigated. The effects of co-delivery of shMDR1 and gefitinib in nanoparticles on reversing multidrug resistance were also evaluated by investigating the cytotoxicity, cellular uptake mechanism, and cell apoptosis on established gefitinib-resistant cells. The results demonstrated that chitosan nanoparticles entrapping gefitinib and shMDR1 had the potential to overcome the multidrug resistance and improve cancer treatment efficacy, especially toward resistant cells. Keywords: P-glycoprotein, nanodelivery system, chemotherapy, gene
format article
author Yu XW
Yang G
Shi YJ
Su C
Liu M
Feng B
Zhao L
author_facet Yu XW
Yang G
Shi YJ
Su C
Liu M
Feng B
Zhao L
author_sort Yu XW
title Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance
title_short Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance
title_full Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance
title_fullStr Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance
title_full_unstemmed Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance
title_sort intracellular targeted co-delivery of shmdr1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/a0b94ca4acc64a8f90f8c73593f00820
work_keys_str_mv AT yuxw intracellulartargetedcodeliveryofshmdr1andgefitinibwithchitosannanoparticlesforovercomingmultidrugresistance
AT yangg intracellulartargetedcodeliveryofshmdr1andgefitinibwithchitosannanoparticlesforovercomingmultidrugresistance
AT shiyj intracellulartargetedcodeliveryofshmdr1andgefitinibwithchitosannanoparticlesforovercomingmultidrugresistance
AT suc intracellulartargetedcodeliveryofshmdr1andgefitinibwithchitosannanoparticlesforovercomingmultidrugresistance
AT lium intracellulartargetedcodeliveryofshmdr1andgefitinibwithchitosannanoparticlesforovercomingmultidrugresistance
AT fengb intracellulartargetedcodeliveryofshmdr1andgefitinibwithchitosannanoparticlesforovercomingmultidrugresistance
AT zhaol intracellulartargetedcodeliveryofshmdr1andgefitinibwithchitosannanoparticlesforovercomingmultidrugresistance
_version_ 1718399178351050752