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Self-assembled carboxymethyl poly (l-histidine) coated poly (β-amino ester)/DNA complexes for gene transfection

Paper ID Volume ID Publish Year Pages File Format Full-Text
7629 558 2012 15 PDF Available
Title
Self-assembled carboxymethyl poly (l-histidine) coated poly (β-amino ester)/DNA complexes for gene transfection
Abstract

Biomaterials coated polymer/DNA complexes are developed as an efficient non-viral gene delivery system. It is able to circumvent the changes of various biophysical properties of the biomaterials and the corresponding polymer/DNA nanoparticles with covalent linkage. In the present study, we introduced pH-sensitive carboxymethyl poly (l-histidine) (CM-PLH) and poly (β-amino ester) (PbAE) as functional biomaterials to form CM-PLH/PbAE/DNA core-shell ternary complexes system based on electrostatically adsorbed coatings for gene efficient delivery and transfection. The preparation of the complexes was performed self-assembly in 25 mm sodium acetate buffer solution at pH 5.2. The complexes kept stable nano-size, behaving good condensation capacity and low toxicity, even provided a higher transfection efficiency than the binary complexes (PbAE/DNA without CM-PLH) and transfected up to (89.6 ± 4.45) % in HEK293 and (57.1 ± 2.10) % in B16-F10 in vitro. The ternary complexes significantly enhanced their cellular uptake and endosomal escape which were proved by the results that the complexes could evade the endosomal lumen and localize in the nucleus of treated cells visualized under Fluorescence Confocal Microscopy (FCM). The aforementioned results indicated that CM-PLH with pH-sensitive imidazole groups played an important role in enhancing the endosomal escape and transfection efficiency. The in vivo gene transfection confirmed that the ternary complexes with pGL3-promoter as led to effectively deposit at the tumor site by the EPR effect and shown 4 fold higher luciferase expression in B16-F10 tumor than the binary complexes. Consequently, CM-PLH/PbAE/DNA ternary complexes system exhibited significant improvements in transfection efficiency in comparison with non-coated PbAE/DNA both in vitro and in vivo, highlighting their functional prospect. Our approach and the gene delivery system fabrication could potentially be useful for effective gene delivery and therapies to targeted cells.

Keywords
Self-assembly; Non-viral vector; Carboxymethyl poly (l-histidine); Poly (β-amino ester); Ternary complexes
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Self-assembled carboxymethyl poly (l-histidine) coated poly (β-amino ester)/DNA complexes for gene transfection
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 2, January 2012, Pages 644–658
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us