Sophora flavescens-derived extracellular vesicles loaded with oncolytic vaccinia virus/IR1061 for NIR-II photoacoustic imaging guided multimodal treatment of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, characterized by high heterogeneity and significant clinical challenges. Despite the widespread adoption of the R-CHOP regimen as the standard treatment, approximately 30 %-40 % of patients experience relapse, necessitating the development of novel therapeutic strategies. Here, we presented a multifunctional therapeutic platform combining oncolytic vaccinia virus (OVV) and the second near-infrared (NIR-II) Fluorescent Dye IR1061, encapsulated within Sophora flavescens-derived extracellular vesicles (SFNPs), termed SFOVV@IR1061. The OVV exhibits selective tropism for tumor cells, inducing targeted lysis while concurrently stimulating robust antitumor immune responses. In parallel, IR1061 serves a dual function, showing high-resolution tumor visualization through photoacoustic imaging while simultaneously enabling precise photothermal therapy (PTT) via its exceptional photothermal conversion efficiency. Utilizing SFNPs as a bioinspired coating improves the stability and tumor-targeting efficiency of OVV while mitigating off-target effects. In vitro and in vivo studies demonstrate that SFOVV@IR1061 effectively promotes tumor cell Apoptosis by inducing immunogenic cell death (ICD) and activating innate and adaptive immune responses. The synergistic combination of OVV-mediated oncolysis and IR1061-driven PTT enhance the therapeutic efficacy and minimize systemic toxicity, which underscores the potential of SFOVV@IR1061 as a promising multimodal therapeutic approach for improving outcomes in DLBCL treatment.