Blockade of metastasis by targeting circulating tumor cells with platelet encapsuled oncolytic adenovirus.

Host immune elimination largely limits the application of oncolytic viruses in clinics. Here, we rationally design a bioactive platelet-based oncolytic adenovirus delivery system. Upon loading adenoviruses, platelets are transformed to a pro-endocytosis status, which facilitates their internalization by circulating tumor cells (CTCs). The CTCs are enriched into metastatic organs by tumor homing effect. The internalized adenoviruses de-coat cover and initiate their oncolytic life cycle, leading to a vigorous immunogenic cell death (ICD) in the metastatic niche. In both a spontaneous metastasis model and a tail vein injection-based CTC dissemination model, intravenous administration of adenovirus-loaded platelets significantly inhibits lung metastasis. Remarkably, this regimen successfully evokes the host immune system in the metastatic organ by inducing tumor ICD. In conclusion, our bioactive delivery system not only largely resolves the bottleneck problem of oncolytic virus application but also provides a foundation for joint immune therapy in clinics.