Partment of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical College, Boston, MA 02115, USA; and 4Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA(Received 25 February 2017; accepted 14 August 2017; published on the internet 30 August 2017) Associate Editor Michael R. King oversaw the evaluation of this article.Abstract Introduction–Gold nanoparticles are versatile carriers for delivery of biomacromolecules. Here, we’ve got developed spiky gold nanoparticles (SGNPs) that can effectively deliver immunostimulatory agents. Objectives–Our objective was to create a platform technology for co-delivery of numerous adjuvant molecules for synergistic stimulation and maturation of innate immune cells. Methods–SGNPs were synthesized by a seed-mediated, surfactant-free synthesis approach and incorporated with polyinosinic-polycytidylic acid (pIC) and DNA oligonucleotide containing unmethylated CpG motif (CpG) by an electrostatic layer-by-layer method.Price of 197632-76-1 Adjuvant-loaded SGNP nano-complexes were examined for their biophysicaland biochemical properties and studied for immune activation making use of bone marrow-derived dendritic cells (BMDCs). Results–We have synthesized SGNPs with branched nanospikes layered with pIC and/or CpG. Adjuvant-loaded SGNP nano-complexes promoted cellular uptake with the adjuvants. Importantly, we accomplished spatio-temporal control more than co-delivery of pIC and CpG via SGNPs, which made synergistic enhancement in cytokine release (IL-6, TNF-a) and upregulation of co-stimulatory markers (CD40, CD80, CD86) in BMDCs, compared with pIC, CpG, or their admixtures. Conclusion–SGNPs serve as a versatile delivery platform that makes it possible for flexible and on-demand cargo fabrication for strong activation of innate immune cells. Keywords–Inorganic nanoparticle, Adjuvant, TLR agonist, Vaccine delivery.Address correspondence to James J. Moon, Division of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic mail: [email protected] Dr. James Moonis John Gideon Searle Assistant Professor within the Division of Pharmaceutical Sciences and Biomedical Engineering at the University of Michigan, Ann Arbor. His translational study program aims to develop novel engineering tools for enhancing vaccines and immunotherapies. His function has been published in Nature Materials, Nature Medicine, PNAS, ACS Nano, and Sci Transl Med, and led to two new biotech businesses, Vedantra Pharmaceuticals (Cambridge, MA) and EVOQ Therapeutics (Ann Arbor, MI) that concentrate on clinical translation of new nano-vaccine technologies. Dr. Moon has received many awards, such as 2017 Emerald Foundation Distinguished Investigator Award, 2016 National Science Foundation Profession Award, 2016 DODCDMRP Career Development Award, and 2015 Melanoma Analysis Alliance Young Investigator Award.22112-84-1 Data Sheet Dr.PMID:31085260 Moon received his B.S. in Bioengineering from University of California, Berkeley, obtained his Ph.D. in Bioengineering from Rice University with Prof. Jennifer West, and completed his postdoctoral coaching with Prof. Darrell Irvine at MIT. This short article is component from the 2017 CMBE Young Innovators special concern.1865-5025/17/1000-0341/2017 Biomedical Engineering SocietyNAM et al.ABBREVIATIONS BMDC CLR CpG DMSO EDC Bone-marrow derived dendritic cell C-type lectin receptor Oligonucleotide containing unmethylated CpG motif Dimethyl sulfoxide 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide Gold nanoparticle Gel permeation chromatography Melanoma diffe.