title: Ternary complexes of amphiphilic polycaprolactone-graft-poly (N,N-dimethylaminoethyl methacrylate), DNA and polyglutamic acid-graft-poly(ethylene glycol) for gene delivery.
abstract: Binary complexes of cationic polymers and DNA were used commonly for DNA delivery, whereas, the excess cationic charge of the binary complexes mainly leads to high toxicity and unstability in vivo. In this paper, ternary complexes by coating polyglutamic acid-graft-poly(ethylene glycol)(PGA-g-mPEG) onto binary complexes of polycaprolactone-graft-poly(N,N-dimethylaminoethyl methacrylate) (PCL-g-PDMAEMA) nanoparticles (NPs)/DNA were firstly developed for effective and targeted gene delivery. The coating of PGA-g-mPEG was able to decrease the zeta potential of the nano-sized DNA complexes nearly to electroneutrality without interferring with DNA condensation ability. As a result, the stability, the escape ability from endosomes and the transfection efficiency of the complexes were enhanced. The ternary complexes of PCL-g-PDMAEMA NPs/DNA/PGA-g-mPEG demonstrated lower cytotoxicity in CCK-8 measurements and higher gene transfection efficiency than the binary complexes in vitro. In addition, Lactate dehydrogenase (LDH) assay was performed to quantify the membrane-damaging effects of the complexes, which is consistent with the conclusion of CCK-8 measurement for cytotoxicity assay. The in vivo imaging measurement and histochemical analysis of tumor sessions confirmed that the intravenous administration of the ternary complexes with red fluorescent protein (RFP) as payload led to protein expression in tumor, which was further enhanced by the targeted coating of PGA-g-PEG-folate.
authors: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors: Shutao
authors: S
authors: Guo
authors: Yuanyu
authors: Y
authors: Huang
authors: Wendi
authors: W
authors: Zhang
authors: Weiwei
authors: W
authors: Wang
authors: Tuo
authors: T
authors: Wei
authors: Daoshu
authors: D
authors: Lin
authors: Jinfeng
authors: J
authors: Xing
authors: Liandong
authors: L
authors: Deng
authors: Quan
authors: Q
authors: Du
authors: Zicai
authors: Z
authors: Liang
authors: Xing-Jie
authors: XJ
authors: Liang
authors: Anjie
authors: A
authors: Dong
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry*; D012844:Sincalide / Q000378:metabolism
chemical_list: D008689:Methacrylates; D011091:Polyesters; C016240:polycaprolactone; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D004247:DNA; D012844:Sincalide; C049840:2-(dimethylamino)ethyl methacrylate