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.
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ABSTRACT: Coating the polycation/DNA binary complexes with PEGylated polyanions can improve long-circulation and biocompatibility in vivo. However, it has been certificated PEG dilemma can reduces gene transfection efficiency because of inhibition in cellular uptake and endosomal escape. Herein, two PEGylated anionic polymers, PEGylated hyaluronic acid (HgP) and PEGylated polyglutamic acid (PGgP) were synthesized to coat the binary complexes of core-shell cationic polycaprolactone-graft-poly (N, N-dimethylaminoethyl methacrylate) nanoparticles/DNA (NP-D). The effects of polyanion structure were evaluated in terms of particle size, zeta potential, cytotoxicity, cellular uptake and transfect efficiency in vitro and in vivo. In vitro study illustrated that HgP coated complexes showed better efficiencies in both cell uptake and transfection than PGgP coated complexes. The coating of HgP on NP-D improved the biocompatibility without reduction in cell uptake and transfection efficacy, and resulted in higher accumulation and gene expression in tumor after IV injection. The success of HgP coating in overcoming PEG dilemma is attributed to the hyaluronic acid (HA)-receptor-mediated endocytosis and outer shell-detachment through the hyaluronidases catalyzed degradation of HA. These results demonstrated that HgP was a promising anionic polymer for coating the polycation/DNA complexes and ternary complexes (HgP coated NP-D) hold promising potential for cancer therapy.Biomaterials 05/2013; · 7.60 Impact Factor
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ABSTRACT: A group of amphiphilic cationic polymers, methoxy polyethylene glycol-block-(polycaprolactone-graft-poly(2-(dimethylamino)ethyl methacrylate)) (PECD), were synthesized by combining ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) methods to form nanoparticles (NPs). The structures of these amphiphilic cationic polymers were characterized by (1)H NMR measurement. The PECD NPs have hydrophobic cores covered with hydrophilic PEG and cationic PDMAEMA chains. These self-assembly nanoparticles were characterized by dynamic light scattering (DLS) technique. PECD NPs can effectively condense DNA to form compact complexes of the size 65-160 nm suitable for gene delivery. The in vitro gene transfection studies of HeLa and HepG2 cells show that PECD NPs have better transfection efficiency compared to polyethylenimine (PEI) and Lipofectamine 2000 at low dose (N/P = 5). The cytotoxicity result shows that PECD NPs/DNA complexes at the optimal N/P ratio for transfection have comparable toxicity with PEI and Lipofectamine. These results indicate that PECD NPs have a great potential to be used as efficient polymeric carriers for gene transfection.Biomaterials 10/2010; 32(3):879-89. · 7.60 Impact Factor
- Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).