Amphiphilic core-shell nanoparticles with poly(ethylenimine) shells as potential gene delivery carriers.
Spherical, well-defined core-shell nanoparticles that consist of poly(methyl methacrylate) (PMMA) cores and branched poly(ethylenimine) shells (PEI) were synthesized via a graft copolymerization of methyl methacrylate from branched PEI induced by a small amount of tert-butyl hydroperoxide. The PMMA-PEI core-shell nanoparticles were between 130 to170 nm in diameter and displayed zeta-potentials near +40 mV at pH 7 in 1 mM aqueous NaCl. Plasmid DNA (pDNA) was mixed with nanoparticles and formed complexes of approximately 120 nm in diameter and was highly monodispersed. The complexes were characterized with respect to their particle size, zeta-potential, surface morphology, and DNA integrity. The complexing ability of the nanoparticles was strongly dependent on the molecular weight of the PEI and the thickness of the PEI shells. The stability of the complexes was influenced by the loading ratio of the pDNA and the nanoparticles. The condensed pDNA in the complexes was significantly protected from enzymatic degradation by DNase I. Cytotoxity studies using MTT colorimetric assays suggested that the PMMA-PEI (25 kDa) core-shell nanoparticles were three times less toxic than the branched PEI (25 kDa). Their transfection efficiencies were also significantly higher. Thus, the PEI-based core-shell nanoparticles show considerable potential as carriers for gene delivery.
Zhu
Junmin
J
Department of Applied Biology and Chemical Technology, Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The Hong Kong Polytechnic University, Hung Hom, Kowloon, PR China.
Tang
Angie
A
Law
Lai Pang
LP
Feng
Min
M
Ho
Kin Man
KM
Lee
Daniel K L
DK
Harris
Frank W
FW
Li
Pei
P
D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D016503:Drug Delivery Systems; D004355:Drug Stability; D004563:Electrochemistry; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D020366:Methylmethacrylate / Q000737:chemistry*; D008970:Molecular Weight; D036103:Nanotechnology; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
D020366:Methylmethacrylate; D011094:Polyethyleneimine; D004247:DNA; D003850:Deoxyribonuclease I