Ovalbumin-loaded paramagnetic nano-triangles for enhanced dendritic cell stimulation, T1-MR imaging, and antitumor immunity

Abstract

Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics. Although the efficiencies of vaccines are limited, they can be enhanced by a well-designed antigen delivery system that promotes sufficient antigen presentation of dendritic cells (DCs) for initiating high T cell immunity. Herein, antigen-loaded manganese oxide (Mn3O4) triangular-shaped ultrasmall nanoparticles were prepared to stimulate DC-based immunotherapy under the guidance of T1 magnetic resonance imaging. The FDA-approved triblock copolymer Pluronic® F-68 was used not only to transfer the phase from hydrophobic to hydrophilic but also to enrich antigen loading and improve the biocompatibility of the prepared nanoparticles. Ovalbumin (OVA), a model antigen, was adsorbed on the surface of polymer-coated nanoparticles through electrostatic interaction to form Mn3O4@PF68-OVA nanoparticle-antigen complexes to stimulate DC-based immunization and antigen-specific T cell immunity. The Mn3O4@PF68-OVA nanovaccine (NV) induces negligible toxicity effects against 4T1 and bone marrow-derived dendritic cells (BMDCs) by conventional methods supports the proliferation of intestine organoids, which are an innovative three-dimensional cytotoxicity evaluation system, thereby indicating their potential safety for in vivo cancer therapies. The designed paramagnetic nanovaccine possessed excellent OVA delivery to dendritic-regulated antigen-specific T cells in vitro by stimulating the maturation level of BMDCs. In addition, Mn3O4@PF68-OVA NVs enhance immunity in vivo by increasing the T-cells and M1 macrophages, which suggests improved immunity. Excitingly, vaccination with Mn3O4@PF68-OVA offer complete protection in the prophylactic group and significant tumor inhibition in the therapeutic group against B16-OVA tumor. In addition, the designed nanovaccine demonstrated high T1-MR imaging in the tumor, further justifying enhanced tumor accumulation and capability to real-time monitor the treatment procedure. This study presents a promising nanosystem to design an effective nanovaccine for T1-MR imaging-guided tumor immunotherapy.