Synthesis and properties of Polycaprolactone-graft-Poly(2-(dimethylamino)ethyl methacrylate-co-methoxy polyethylene glycol monomethacrylate) as non-viral gene vector
ABSTRACT Polycaprolactone-graft-Poly(2-(dimethylamino)ethyl methacrylate-co-methoxy polyethylene glycol monomethacrylate) (PCL-graft-P(DMAEMA-co-mPEGMMA)) was synthesized by combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). PCL-graft-P(DMAEMA-co-mPEGMMA) was characterized by FTIR, 1H NMR, and GPC. PCL-graft-P(DMAEMA-co-mPEGMMA) with expected composition and structure was achieved. pH- and thermo-sensitive properties of the PCL-graft-P(DMAEMA-co-mPEGMMA) nanoparticles prepared by the nanoprecipitation method were investigated by TEM and DLS. With increase in the temperature, the size of PCL-graft-P(DMAEMA-co-mPEGMMA) nanoparticles is decreased under base environment. Furthermore, in vitro transfection and toxicity assays were tested in 293T cells. The results indicate that PCL-graft-P(DMAEMA-co-PEGMMA) has lower cytotoxicity at N/P ratios less than 10 with transfection efficiency concomitantly reducing at N/P ratios less than 20 compared to PCL-graft-PDMAEMA as the control. However, PCL-graft-P(DMAEMA-co-PEGMMA) presents higher transfection efficiency at N/P ratios more than 20 compared to PCL-graft-PDMAEMA. Copyright © 2010 John Wiley & Sons, Ltd.
SourceAvailable from: Tingbin Zhang[Show abstract] [Hide abstract]
ABSTRACT: The low transfection efficiency of polycations is still a major problem for successful gene therapy. To address this issue, in this study, hydrophilic poly(vinyl pyrrolidone)-graft-poly[2-(N,N-dimethylamino)ethyl methacrylate] (PVP-g-PDMAEMA) and amphiphilic poly(vinyl pyrrolidone)-graft-poly[2-(N,N-dimethylamino)ethyl methacrylate]-block-poly(methylmethacrylate) (PVP-g-PDMAEMA-b-PMMA) were synthesized via atom transfer radical polymerization (ATRP) method, and their properties as gene vectors were investigated subsequently. PVP-g-PDMAEMA formed random coil in water and PVP-g-PDMAEMA-b-PMMA self-assembled into spherical core-shell micelle with a very low critical micelle concentration of only 6.3 × 10-3 mg mL-1. PVP-g-PDMAEMA-b-PMMA/pDNA polyplexes performed excellent gene transfection efficiency, which showed not only much higher gene transfection efficiency than PVP-g-PDMAEMA/pDNA polyplexes, but obviously surpassed 25k PEI at N/P ratio around 3 on 293T cell lines. Hence, the results suggested that PVP-g-PDMAEMA-b-PMMA could be a highly efficient gene vector.11/2014; 3(5). DOI:10.1039/C4TB01754D
[Show abstract] [Hide abstract]
ABSTRACT: The controlled ring-opening polymerisation (ROP) of an ε-caprolactone derivative that contains an ATRP initiator pendant to the ring, γ-(2-bromo-2-methyl propionyl)-ε-caprolactone (γ-BMPCL), and its copolymerisation with ε-caprolactone (CL) is reported. Functional PCL copolymers that contained pendant ATRP initiators were obtained with higher than previously reported molecular weights using diphenyl phosphate (DPP) as the catalyst at room temperature. Surface-initiated ATRP grafting of oligo(ethylene glycol) methacrylate was successfully carried out on the surface of two dimensional (2D) substrates comprising thin films of a functional PCL copolymer.03/2014; 5(8). DOI:10.1039/C3PY01701J
[Show abstract] [Hide abstract]
ABSTRACT: Due to their biodegradable character, polyesters such as polycaprolactone (PCL), poly(d,l-lactide) (PDLLA), and polylactic-co-glycolic acid (PLGA) were widely used as the hydrophobic cores of amphiphilic cationic nanoparticles (NPs) for siRNA delivery. However, fewer researches focused on facilitating siRNA delivery by adjusting the polyester composition of these nanoparticles. Herein, we investigated the contribution of polyester segments in siRNA delivery in vitro by introducing different ratio of DLLA moieties in PCL segments of mPEG-block-PCL-graft-poly(dimethylamino ethyl methacrylate)(PEG-b-PCL-g-PDMAEMA). It was noticed that compared with the other ratios of DLLA moieties, a certain molar ratio (about 70%) of the NPs, named mPEG45-P(CL21-co-DLLA48)-g-(PDMAEMA29)2 (PECLD-70), showed the highest gene knockdown efficiency but poorest cellular uptake ability in vitro. Further research revealed that NPs with various compositions of the polyester cores showed different physicochemical properties including particle size, zeta potential and stiffness, leading to different endocytosis mechanisms thus influencing the cellular uptake efficiency. Subsequently, we observed that the cells treated by PECLD-70 NPs/Cy5 siRNA complexes exhibited more diffuse Cy5 signal distribution than other NPs by confocal laser scanning microscope, which suggested that siRNA delivered by PECLD-70 NPs/Cy5 siRNA complexes possessed of stronger capabilities in escaping from endosome/lysosome, entering the RNA-induced silencing complex (RISC) and cutting the target mRNA efficiently. The different siRNA release profile was dominated by the degradation rate of polyester segments. Therefore, it could be concluded that the adjustment of hydrophobic core of cationic nanoparticles could significantly affect their transfection behavior and appropriate polyester composition should be concerned in designing of analogous siRNA vectors. Copyright © 2015 Elsevier Ltd. All rights reserved.Biomaterials 04/2015; 48. DOI:10.1016/j.biomaterials.2015.01.026 · 8.31 Impact Factor