Scavenger receptors mediate cellular uptake of polyvalent oligonucleotide-functionalized gold nanoparticles.
Mammalian cells have been shown to internalize oligonucleotide-functionalized gold nanoparticles (DNA-Au NPs or siRNA-Au NPs) without the aid of auxiliary transfection agents and use them to initiate an antisense or RNAi response. Previous studies have shown that the dense monolayer of oligonucleotides on the nanoparticle leads to the adsorption of serum proteins and facilitates cellular uptake. Here, we show that serum proteins generally act to inhibit cellular uptake of DNA-Au NPs. We identify the pathway for DNA-Au NP entry in HeLa cells. Biochemical analyses indicate that DNA-Au NPs are taken up by a process involving receptor-mediated endocytosis. Evidence shows that DNA-Au NP entry is primarily mediated by scavenger receptors, a class of pattern-recognition receptors. This uptake mechanism appears to be conserved across species, as blocking the same receptors in mouse cells also disrupted DNA-Au NP entry. Polyvalent nanoparticles functionalized with siRNA are shown to enter through the same pathway. Thus, scavenger receptors are required for cellular uptake of polyvalent oligonucleotide functionalized nanoparticles.
Interdepartmental Biological Sciences Program, Department of Chemistry, and International Institute for Nanotechnology, Northwestern University, Evanston, Illinois, USA.
Pinal C
PC
Patel
David A
DA
Giljohann
Weston L
WL
Daniel
Dan
D
Zheng
Andrew E
AE
Prigodich
Chad A
CA
Mirkin
D000818:Animals; D001692:Biological Transport; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006046:Gold / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry* / Q000493:pharmacokinetics*; D011069:Poly I / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013046:Specific Gravity; D014168:Transferrin / Q000378:metabolism
D009841:Oligonucleotides; D011134:Polysaccharides; D034741:RNA, Small Interfering; D051116:Receptors, Scavenger; D014168:Transferrin; D011069:Poly I; D012710:Serum Albumin, Bovine; D006046:Gold; D004247:DNA; C007789:fucoidan