Characterization of nickel-decorated PLGA particles anchored with a his-tagged polycation.
The pharmacological impact of oligodeoxynucleotides (ODN) as transcription factors decoys (anti-sense) depends on the efficiency of cellular uptake. In this study, we sought to generate nickel-decorated particles to facilitate the entry of ODN into dendritic cells (DCs), the primary instigators of immune responses. Nickel ions were incorporated into the matrix of poly(D,L-lactide-co-glycolide) (PLGA) particles using the metal chelating lipid DOGS-NTA-Ni. Submicrometer-sized PLGA particles containing nickel ions (PLGA-Ni) were formed using a double-emulsion solvent evaporation method. Infrared spectroscopy provided chemical proofs of nickel incorporation into the PLGA matrix. Binding of the polycation O10H6 raised the surface potential of PLGA-Ni from -17 mV to +13 mV. This change was partially reserved by the presence of free imidazole, suggesting the binding was mediated by nickel-histidine coordination. When compared to PLGA particles without nickel, ODN bound to O10H6-coated PLGA-Ni particles exhibited enhanced capacity to accumulate in DCs cultured in vitro. DCs exhibited cellular stress after exposure to PLGA-Ni complexed with O10H6 and DNA, but this effect can be prevented by serum and was reversed overnight. These data suggest PLGA-Ni should be further explored as a nucleic acid carrier in the context of anti-sense gene down-regulation.
Kovacs
Jeffrey R
JR
Division of Pharmaceutical Sciences, Duquesne University, Mellon Hall 413, Pittsburgh, PA 15282, USA.
Tidball
Jenny
J
Ross
Anthony
A
Jia
Liang
L
Zheng
Ying
Y
Gawalt
Ellen S
ES
Meng
Wilson S
WS
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002412:Cations / Q000737:chemistry; D002463:Cell Membrane Permeability; D002614:Chelating Agents; D003713:Dendritic Cells / Q000166:cytology*; D004337:Drug Carriers / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D009532:Nickel / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties
D002412:Cations; D002614:Chelating Agents; D004337:Drug Carriers; D009838:Oligodeoxyribonucleotides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006639:Histidine; D009532:Nickel