Targeted Codelivery of an Antigen and Dual Agonists by Hybrid Nanoparticles for Enhanced Cancer Immunotherapy

Among approaches of current cancer immunotherapy, a dendritic cell (DC)-targeted vaccine based on nanotechnology could be a promising way to efficiently induce potent immune responses. To enhance DC targeting and vaccine efficiency, we included imiquimod (IMQ), a toll-like receptor 7/8 (TLR 7/8) agonist, and monophosphoryl lipid A (MPLA), a TLR4 agonist, to synthesize lipid-polymer hybrid nanoparticles using PCL–PEG-PCL and DOTAP (IMNPs) as well as DSPE-PEG-mannose (MAN-IMNPS). The spatiotemporal delivery of MPLA (within the outer lipid layer) to extracellular TLR4 and IMQ (in the hydrophobic core of NPs) to intracellular TLR7/8 can activate DCs synergistically to improve vaccine efficacy. Ovalbumin (OVA) as a model antigen was readily absorbed by positively charged DOTAP and showed a quick release in vitro. Our results demonstrated that this novel nanovaccine enhanced cellular uptake, cytokine production, and maturation of DCs. Compared with the quick metabolism of free OVA-agonists, the depot effect of ...