Regulating immune response using polyvalent nucleic acid-gold nanoparticle conjugates.
The immune response of macrophage cells to internalized polyvalent nucleic acid-functionalized gold nanoparticles has been studied. This study finds that the innate immune response (as measured by interferon-beta levels) to densely functionalized, oligonucleotide-modified nanoparticles is significantly less (up to a 25-fold decrease) when compared to a lipoplex carrying the same DNA sequence. The magnitude of this effect is inversely proportional to oligonucleotide density. It is proposed that the enzymes involved in recognizing foreign nucleic acids and triggering the immune response are impeded due to the local surface environment of the particle, in particular high charge density. The net effect is an intracelluar gene regulation agent that elicits a significantly lower cellular immune response than conventional DNA transfection materials.
Massich
Matthew D
MD
Department of Chemistry, International Institute for Nanotechnology, Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 633 Clark Street, Evanston, Illinois 60208, USA.
Giljohann
David A
DA
Seferos
Dwight S
DS
Ludlow
Louise E
LE
Horvath
Curt M
CM
Mirkin
Chad A
CA
D000818:Animals; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006046:Gold; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016899:Interferon-beta / Q000378:metabolism; D053768:Metal Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D051379:Mice; D036103:Nanotechnology / Q000379:methods; D009696:Nucleic Acids / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009696:Nucleic Acids; D006046:Gold; D016899:Interferon-beta