title: Gold nanoparticle delivery of modified CpG stimulates macrophages and inhibits tumor growth for enhanced immunotherapy.
abstract: Gold nanoparticle accumulation in immune cells has commonly been viewed as a side effect for cancer therapeutic delivery; however, this phenomenon can be utilized for developing gold nanoparticle mediated immunotherapy. Here, we conjugated a modified CpG oligodeoxynucleotide immune stimulant to gold nanoparticles using a simple and scalable self-assembled monolayer scheme that enhanced the functionality of CpG in vitro and in vivo. Nanoparticles can attenuate systemic side effects by enhancing CpG delivery passively to innate effector cells. The use of a triethylene glycol (TEG) spacer on top of the traditional poly-thymidine spacer increased CpG macrophage stimulatory effects without sacrificing DNA content on the nanoparticle, which directly correlates to particle uptake. In addition, the immune effects of modified CpG-AuNPs were altered by the core particle size, with smaller 15 nm AuNPs generating maximum immune response. These TEG modified CpG-AuNP complexes induced macrophage and dendritic cell tumor infiltration, significantly inhibited tumor growth, and promoted survival in mice when compared to treatments with free CpG.
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas, United States of America.
authors.forename: Adam Yuh
authors.initials: AY
authors.lastname: Lin
authors.forename: Joao Paulo Mattos
authors.initials: JP
authors.lastname: Almeida
authors.forename: Adham
authors.initials: A
authors.lastname: Bear
authors.forename: Nathan
authors.initials: N
authors.lastname: Liu
authors.forename: Laureen
authors.initials: L
authors.lastname: Luo
authors.forename: Aaron Edward
authors.initials: AE
authors.lastname: Foster
authors.forename: Rebekah Anna
authors.initials: RA
authors.lastname: Drezek
mesh_terms: D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D018899:CpG Islands; D017931:DNA Primers; D006046:Gold / Q000737:chemistry*; D007167:Immunotherapy; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D017931:DNA Primers; D006046:Gold