Document Detail


P-glycoprotein antibody functionalized carbon nanotube overcomes the multidrug resistance of human leukemia cells.
MedLine Citation:
PMID:  20148593     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multidrug resistance (MDR), which is related to cancer chemotherapy, tumor stem cells, and tumor metastasis, is a huge obstacle for the effective cancer therapy. One of the underlying mechanisms of MDR is the increased efflux of anticancer drugs by overexpressed P-glycoprotein (P-gp) of multidrug resistant cells. In this work, the antibody of P-gp (anti-P-gp) functionalized water-soluble single-walled carbon nanotubes (Ap-SWNTs) loaded with doxorubicin (Dox), Dox/Ap-SWNTs, were synthesized for challenging the MDR of K562 human leukemia cells. The resulting Ap-SWNTs could not only specifically recognize the multidrug resistant human leukemia cells (K562R), but also demonstrate the effective loading and controllable release performance for Dox toward the target K562R cells by exposing to near-infrared radiation (NIR). The recognition capability of Ap-SWNTs toward the K562R cells was confirmed by flow cytometry (FCM) and confocal laser scanning microscopy (CLSM). The binding affinity of Ap-SWNTs toward drug-resistant K562R cells was ca. 23-fold higher than that toward drug-sensitive K562S cells. Additionally, CLSM indicated that Ap-SWNTs could specifically localize on the cell membrane of K562R cells and the fluorescence of Dox in K562R cells could be significantly enhanced after the employment of Ap-SWNTs as carrier. Moreover, the composite of Dox and Ap-SWNTs (Dox/Ap-SWNTs) expressed 2.4-fold higher cytotoxicity and showed the significant cell proliferation suppression toward K562R leukemia cells (p < 0.05) as compared with free Dox which is popularly employed in clinic trials. These results suggest that the Ap-SWNTs are the promising drug delivery vehicle for overcoming the MDR induced by the overexpression of P-gp on cell membrane. Ap-SWNTs loaded with drug molecules could be used to suppress the proliferation of multidrug resistant cells, destroy the tumor stem cells, and inhibit the metastasis of tumor.
Authors:
Ruibin Li; Ren'an Wu; Liang Zhao; Minghuo Wu; Ling Yang; Hanfa Zou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  ACS nano     Volume:  4     ISSN:  1936-086X     ISO Abbreviation:  ACS Nano     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-23     Completed Date:  2010-06-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101313589     Medline TA:  ACS Nano     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1399-408     Citation Subset:  IM    
Affiliation:
National Chromatographic R&A Center, CAS Key Laboratory of Separation Sciences for Analytical Chemistry,Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023, China.
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MeSH Terms
Descriptor/Qualifier:
Antibodies / chemistry*,  immunology*
Biological Transport
Cell Survival / drug effects
Doxorubicin / chemistry,  metabolism,  pharmacology
Drug Carriers / chemistry*,  metabolism
Drug Resistance, Multiple / drug effects*
Humans
Intracellular Space / metabolism
K562 Cells
Leukemia / drug therapy*,  pathology
Nanotubes, Carbon / chemistry*
P-Glycoprotein / immunology*,  metabolism
Chemical
Reg. No./Substance:
0/Antibodies; 0/Drug Carriers; 0/Nanotubes, Carbon; 0/P-Glycoprotein; 23214-92-8/Doxorubicin

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