To accomplish effective cancer imaging and integrated therapy, the multifunctional nanotheranostic Fe₃O₄-MTX@HBc core-shell nanoparticles (NPs) were designed. A straightforward method was demonstrated for efficient encapsulation of magnetic NPs into the engineered virus-like particles (VLPs) through the affinity of histidine tags for the methotrexate (MTX)-Ni²⁺ chelate. HBc₁₄₄-His VLPs shell could protect Fe₃O₄-MTX NPs from the recognition by the reticuloendothelial system as well as could increase their cellular uptake efficiency. Through our well-designed tactic, the photothermal efficiency of Fe₃O₄ NPs were obviously improved in vitro and in vivo upon near-infrared (NIR) laser irradiation. Moreover, Magnetic resonance imaging (MRI) results showed that the Fe₃O₄-MTX@HBc core-shell NPs were reliable T₂-type MRI contrast agents for tumor imaging. Hence the Fe₃O₄-MTX@HBc core-shell NPs may act as a promising theranostic platform for multimodal cancer treatment.

Different types of vaccines have been developed to elicit active immunization to treat various diseases, while suffer from limitation of efficacy. Herein, a novel immunostimulatory nanocomposite (CpG-Au@HBc VLP) was rationally designed by self-assembling engineered virus-like particles encapsulating CpG-gold nanoparticle conjugates through electrostatic interactions. The monodispersed and uniformly sized CpG-Au@HBc VLP showed increased CD4+, CD8+ T cell numbers and stronger secretion of cytokine interferon-gamma than HBc VLPs adjuvanted with conventional Freund’s adjuvant. Furthermore, the use of Au nanoparticles also generated enhanced immunogenicity of CpG and VLPs on both humoral and cellular immune pathways, as followed from increased expressions of total HBc-specific antibody titer, CD4+ T cells, CD8+ T cells, cytokine interleukin-4, and interferon-gamma. These findings demonstrated that CpG-Au@HBc VLP nanocomposite could induce robust cellular and humoral immune response, which could be a potential vaccine for future prophylactic and therapeutic application.