Functionalized Layered Double Hydroxide Nanoparticles Conjugated with Disulfide-Linked Polycation Brushes for Advanced Gene Delivery

Layered double hydroxides (LDHs) have aroused great attention as potential nanosized drug delivery carriers, but independent inorganic LDH wrapped with DNA shows very low transfection efficiency. To manipulate and control the surface properties of LDH nanoparticles is of crucial importance in the de...

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Bibliographic Details
Published in:Bioconjugate chemistry 2013-06, Vol.24 (6), p.968-978
Main Authors: Hu, H, Xiu, K. M, Xu, S. L, Yang, W. T, Xu, F. J
Format: Article
Language:English
Subjects:
Animals
Cations - chemistry
Cations - pharmacology
Cell Survival - drug effects
Cells
Cercopithecus aethiops
Chemical bonds
COS Cells
Disulfides - chemistry
Disulfides - pharmacology
DNA - chemistry
Dose-Response Relationship, Drug
Gene Transfer Techniques
Genes
Genetic Vectors - chemistry
Genetic Vectors - pharmacology
Hep G2 Cells
Humans
Hydroxides - chemistry
Hydroxides - pharmacology
Nanoparticles
Nanoparticles - chemistry
Particle Size
Plasmids
Polymers - chemistry
Polymers - pharmacology
Structure-Activity Relationship
Surface Properties
Temperature
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Summary:Layered double hydroxides (LDHs) have aroused great attention as potential nanosized drug delivery carriers, but independent inorganic LDH wrapped with DNA shows very low transfection efficiency. To manipulate and control the surface properties of LDH nanoparticles is of crucial importance in the designing of LDH-based drug carriers. In this work, surface-initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)­ethyl methacrylate (DMAEMA) is employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined novel gene delivery vectors (termed as LDH-PDs), where a flexible three-step method was first developed to introduce the ATRP initiation sites containing disulfide bonds onto LDH surfaces. In comparison the pristine LDH particles, the resultant LDH-PDs exhibited better ability to condense plasmid DNA (pDNA) and much higher levels to delivery genes in different cell lines including COS7 and HepG2 cell lines. Moreover, the LDH-PDs also could largely enhance cellular uptake. This present study demonstrates that functionalization of bioinorganic LDH with flexible polycation brushes is an effective means to produce new LDH-based gene delivery systems.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc300683y