Jutaek Nam1,2, Sejin Son1,2,3, James J Moon1,2,4. 1. Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA. 2. Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. 3. Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. 4. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract
INTRODUCTION: Gold nanoparticles are versatile carriers for delivery of biomacromolecules. Here, we have developed spiky gold nanoparticles (SGNPs) that can efficiently deliver immunostimulatory agents. OBJECTIVES: Our goal was to develop a platform technology for co-delivery of multiple adjuvant molecules for synergistic stimulation and maturation of innate immune cells. METHODS: SGNPs were synthesized by a seed-mediated, surfactant-free synthesis method and incorporated with polyinosinic-polycytidylic acid (pIC) and DNA oligonucleotide containing unmethylated CpG motif (CpG) by an electrostatic layer-by-layer approach. Adjuvant-loaded SGNP nano-complexes were examined for their biophysical and biochemical properties and studied for immune activation using bone marrow-derived dendritic cells (BMDCs). RESULTS: We have synthesized SGNPs with branched nano-spikes layered with pIC and/or CpG. Adjuvant-loaded SGNP nano-complexes promoted cellular uptake of the adjuvants. Importantly, we achieved spatio-temporal control over co-delivery of pIC and CpG via SGNPs, which produced synergistic enhancement in cytokine release (IL-6, TNF-α) 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 allows flexible and on-demand cargo fabrication for strong activation of innate immune cells.
INTRODUCTION: Gold nanoparticles are versatile carriers for delivery of biomacromolecules. Here, we have developed spiky gold nanoparticles (SGNPs) that can efficiently deliver immunostimulatory agents. OBJECTIVES: Our goal was to develop a platform technology for co-delivery of multiple adjuvant molecules for synergistic stimulation and maturation of innate immune cells. METHODS:SGNPs were synthesized by a seed-mediated, surfactant-free synthesis method and incorporated with polyinosinic-polycytidylic acid (pIC) and DNA oligonucleotide containing unmethylated CpG motif (CpG) by an electrostatic layer-by-layer approach. Adjuvant-loaded SGNP nano-complexes were examined for their biophysical and biochemical properties and studied for immune activation using bone marrow-derived dendritic cells (BMDCs). RESULTS: We have synthesized SGNPs with branched nano-spikes layered with pIC and/or CpG. Adjuvant-loaded SGNP nano-complexes promoted cellular uptake of the adjuvants. Importantly, we achieved spatio-temporal control over co-delivery of pIC and CpG via SGNPs, which produced synergistic enhancement in cytokine release (IL-6, TNF-α) 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 allows flexible and on-demand cargo fabrication for strong activation of innate immune cells.
Authors: Alexandre de Titta; Marie Ballester; Ziad Julier; Chiara Nembrini; Laura Jeanbart; André J van der Vlies; Melody A Swartz; Jeffrey A Hubbell Journal: Proc Natl Acad Sci U S A Date: 2013-11-18 Impact factor: 11.205
Authors: Amy Sexton; Paul G Whitney; Siow-Feng Chong; Alexander N Zelikin; Angus P R Johnston; Robert De Rose; Andrew G Brooks; Frank Caruso; Stephen J Kent Journal: ACS Nano Date: 2009-11-24 Impact factor: 15.881
Authors: Christine Trumpfheller; Marina Caskey; Godwin Nchinda; Maria Paula Longhi; Olga Mizenina; Yaoxing Huang; Sarah J Schlesinger; Marco Colonna; Ralph M Steinman Journal: Proc Natl Acad Sci U S A Date: 2008-02-06 Impact factor: 11.205
Authors: Stefan Harmsen; Ruimin Huang; Matthew A Wall; Hazem Karabeber; Jason M Samii; Massimiliano Spaliviero; Julie R White; Sébastien Monette; Rachael O'Connor; Kenneth L Pitter; Stephen A Sastra; Michael Saborowski; Eric C Holland; Samuel Singer; Kenneth P Olive; Scott W Lowe; Ronald G Blasberg; Moritz F Kircher Journal: Sci Transl Med Date: 2015-01-21 Impact factor: 17.956