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Abstract
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.