ArticleInternational journal of nanomedicine2025
Multifunctional HBc Virus-Like Particles Reprogram Immunosuppressive Macrophages and Potentiate CD8
Article in International journal of nanomedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Nanovaccines for lung cancer: Platforms, mechanistic insights, and translational challenges.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Low-affinity binding of anti-B7-H3 clone MJ18 to murine B7-H3 fails to induce tumor regression.Scientific reports · 2026Article
- Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion.Frontiers in immunology · 2026Review
- Evaluation of cellular immune response and biosafety of SV40 virus-like particle in tumor immunotherapy.Journal of materials science. Materials in medicine · 2025Article
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11 authors.
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Abstract
Introduction: Tumor-associated macrophages (TAMs) promote immunosuppression, hindering immune checkpoint blockade and immunotherapy efficacy. To overcome this, we developed a novel multifunctional nanovaccine based on hepatitis B core virus-like particles (HBc VLP) to synergistically remodel the immunosuppressive tumor microenvironment through integrated TAM reprogramming and B7-H3 checkpoint blockade. Methods: The core VLP co-displayed tumor antigen peptide MAGE-A10 and TAM-targeting peptide M2pep via fusion expression. Immunostimulatory CpG oligodeoxynucleotide 1826 (CpG) was encapsulated within VLP. Anti-B7-H3 antibody (αB7-H3) and polyethylene glycol (PEG) were chemically conjugated to the surface for checkpoint blockade and prolonged circulation, forming CpG@VLP-αB7-H3-PEG. Results: Structural characterization using transmission electron microscopy and dynamic light scattering confirmed the hollow spherical self-assembly of VLP. Nanovaccines efficiently targeted TAMs in vitro and in vivo. Following CpG encapsulation (5.60 µg/mg), the nanovaccine reprogrammed M2-like TAMs into an M1-like phenotype. This was achieved by elevating the M1/M2 ratios of CD86/CD206 and MHC II/CD206 to 15.50-fold and 3.11-fold, respectively, as determined by flow cytometry. Further conjugation of αB7-H3 (250 µg/mg) significantly enhanced T-cell activation in TAM-T cell co-culture assays. In B16-F10 melanoma-bearing mice, reprogrammed iNOS Conclusion: This HBc VLP-based nanovaccine constitutes a pioneering multifunctional platform designed to overcome TAM-mediated immunosuppression through synergistic integration of three modalities: antigen presentation, TAM phenotype reprogramming, and B7-H3 checkpoint blockade. To the best of our knowledge, this is the first nanovaccine architecture to enable coordinated immunomodulation. Its modular design supports the clinical translation of solid tumors and personalized immunotherapy.
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