Biomimetic Hybrid Membrane-Cloaked Nanoparticles Assisted with Laser Irradiation for Synergistic Photothermal Immunotherapy of Fibrosarcoma

Fibrosarcoma is a malignant tumor of soft tissues that can occur in various parts of the body. Surgical resection remains the primary treatment, but local recurrence and metastasis are common after surgery. Due to the limited efficacy of surgical interventions and generally poor prognosis, immunotherapy has emerged as a strategy for treating fibrosarcoma. In this study, we fused WEHI-164 fibrosarcoma cell membranes with red blood cell (RBC) membranes to create a hybrid biomimetic coating (WRV). This hybrid membrane was used to encapsulate poly(lactic- co -glycolic) acid (PLGA) nanoparticles containing indocyanine green (ICG) and imiquimod (R837) (PLGA-ICG-R837@WRV, PIR@WRV) for synergistic photothermal and immunotherapy of fibrosarcoma. In a tumor-bearing mouse model, PIR@WRV effectively accumulated at the tumor site, producing superior photothermal effects and eradicating primary tumors. The induced hyperthermia enhanced tumor immunogenicity and facilitated the release of the immune adjuvant R837, further activating immune responses in the mice and simultaneously inhibiting the growth of distant tumors. Moreover, PIR@WRV combined with near-infrared (NIR) light demonstrated potential as a nanovaccine, providing long-term immune memory effects to prevent tumor recurrence. Our research presents a therapeutic strategy for the treatment of nontargeted fibrosarcoma, offering the potential to activate the immune system and inhibit tumor recurrence. This strategy also offers a straightforward and promising approach for treating metastatic cancers and preventing tumor recurrence.