Biomimetic sonodynamic therapy-nanovaccine integration platform potentiates Anti-PD-1 therapy in hypoxic tumors

Immune checkpoint blockade (ICB) therapy has emerged as novel therapeutic modality for hard-to-treat solid tumors. However, inadequate T cell infiltration in hypoxic solid tumors limits its anticancer efficacy. Here we develop a sonodynamic therapy (SDT)-nanovaccine integration platform constructed by binding a manganese porphyrin-based metal-organic frameworks (Mn-MOF) with an immune adjuvant CpG and then coating with cell membranes derived from ovalbumin (OVA)-overexpressing melanoma B16 cells ([email protected]) for potentiating anti-programmed death receptor 1 (PD-1) antibody in malignant melanoma therapy. [email protected] with prolonged blood circulation and enhanced tumor targeting efficiently relieves tumor hypoxia and generates strong SDT effects and immunogenic cell death. The tumor-associated antigens both in situ derived from SDT and OVA exhibit vaccine-like functions together with the immune adjuvant CpG, eliciting a strong tumor-specific immune response by promoting DC maturation and T cell activation. Importantly, the combination of [email protected] SDT and anti-PD-1 antibody induces stronger systemic immune response and long-term immunological memory function to prevent tumor growth and recurrence. These findings reveal that [email protected] with US irradiation may be a potential candidate to potentiate ICB therapy for hypoxic cancer therapy.