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A Polyethylenimine-Containing and Transferrin-Conjugated Lipid Nanoparticle System for Antisense Oligonucleotide Delivery to AML
Joint Authors
Zheng, Yu
Yuan, Yiming
Zhang, Lijing
Cao, Hua
Yang, Yi
Yang, Xiao-juan
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-01-26
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Limited success of antisense oligonucleotides (ASO) in clinical anticancer therapy calls for more effective delivery carriers.
The goal of this study was to develop a nanoparticle system for delivery of ASO G3139, which targets mRNA of antiapoptotic protein Bcl-2, to acute myeloid leukemia (AML) cells.
The synthesized nanoparticle Tf-LPN-G3139 contained a small molecular weight polyethylenimine and two cationic lipids as condensing agents, with transferrin on its surface for selective binding and enhanced cellular uptake.
The optimized nitrogen to phosphate (N/P) ratio was 4 to achieve small particle size and high G3139 entrapment efficiency.
The Tf-LPN-G3139 exhibited excellent colloidal stability during storage for at least 12 weeks and remained intact for 4 hours in nuclease-containing serum.
The cellular uptake results showed extensive internalization of fluorescence-labelled G3139 in MV4-11 cells through Tf-LPN.
Following transfection, Tf-LPN-G3139 at 1 µM ASO level induced 54% Bcl-2 downregulation and >20-fold apoptosis compared to no treatment.
When evaluated in mice bearing human xenograft AML tumors, Tf-LPN-G3139 suppressed tumor growth by ~60% at the end of treatment period, accompanied by remarkable pharmacological effect of Bcl-2 inhibition in tumor.
In conclusion, Tf-LPN-G3139 is a promising nanoparticle system for ASO G3139 delivery to AML and warrants further investigations.
American Psychological Association (APA)
Yuan, Yiming& Zhang, Lijing& Cao, Hua& Yang, Yi& Zheng, Yu& Yang, Xiao-juan. 2016. A Polyethylenimine-Containing and Transferrin-Conjugated Lipid Nanoparticle System for Antisense Oligonucleotide Delivery to AML. BioMed Research International،Vol. 2016, no. 2016, pp.1-8.
https://search.emarefa.net/detail/BIM-1096844
Modern Language Association (MLA)
Yuan, Yiming…[et al.]. A Polyethylenimine-Containing and Transferrin-Conjugated Lipid Nanoparticle System for Antisense Oligonucleotide Delivery to AML. BioMed Research International No. 2016 (2016), pp.1-8.
https://search.emarefa.net/detail/BIM-1096844
American Medical Association (AMA)
Yuan, Yiming& Zhang, Lijing& Cao, Hua& Yang, Yi& Zheng, Yu& Yang, Xiao-juan. A Polyethylenimine-Containing and Transferrin-Conjugated Lipid Nanoparticle System for Antisense Oligonucleotide Delivery to AML. BioMed Research International. 2016. Vol. 2016, no. 2016, pp.1-8.
https://search.emarefa.net/detail/BIM-1096844
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1096844