Synergetic Sonodynamic-Immunotherapy based on phycocyanin nanoparticles (PCNP) reduces tumor growth and metastasis in mice

Abstract

Sonodynamic-immunotherapy as a combined treatment offers a synergistic effect for tumor growth and metastasis reduction. The concise, manufacturable, multifunctional nanosystems are the key to implementing this strategy. In this article, we report the development of a novel nanoscale system based on phycocyanin nanoparticles (PCNP) for the co-delivery of the immunoadjuvant hydrochloride imiquimod (R837(hy)), achieving a dual role as both sonosensitizer and immunomodulatory agent. Our findings demonstrate that PCNP-mediated SDT can trigger immunogenic cell death (ICD) in tumor cells, releasing tumor-associated antigens and simultaneously delivering R837(hy) to effectively activate the immune response. This process results in the maturation of dendritic cells and leading to a potent and targeted antitumor immune response. When combined with the cytotoxic T-lymphocyte antigen 4 (CTLA-4) checkpoint blockade, this strategy significantly reduces tumor growth and metastasis in murine models, with minimal systemic toxicity. Our approach effectively integrates sonodynamics and immunotherapy for the treatment and prevention of cancer recurrence through the PCNP-R837(hy) system, offering a promising strategy to overcome the limitations of current therapies.