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.
| Original language | English |
|---|---|
| Pages (from-to) | 341-355 |
| Number of pages | 15 |
| Journal | Cellular and Molecular Bioengineering |
| Volume | 10 |
| Issue number | 5 |
| DOIs | |
| State | Published - 1 Oct 2017 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2017, Biomedical Engineering Society.
Keywords
- Adjuvant
- Inorganic nanoparticle
- TLR agonist
- Vaccine delivery
