Cold atmospheric plasma boosts oncolytic adenovirus therapy by promoting tumour virus-binding receptors exposure

Oncolytic viruses (OVs) are a promising class of cancer therapeutics, yet their clinical efficacy is frequently limited by inefficient viral entry into tumour cells. OV infection depends on receptor-mediated endocytosis initiated at the cell surface, but key viral entry receptors are often sequestered within intercellular junctions, restricting viral access. Here, we demonstrate that cold atmospheric plasma (CAP), a highly ionized gas enriched with reactive oxygen and nitrogen species, can directly and sustainably disrupt tumour cell junctions, thereby increasing the surface accessibility of viral entry receptors. This physical intervention markedly enhances receptor-mediated OV uptake, achieving over a threefold increase compared with untreated controls in B16F10 cell line. A similar enhancement in viral uptake was also observed in Hepa1-6, HCT116, and A549 cells. In a postoperative B16F10 tumour recurrence model, CAP-potentiated OV therapy outperformed monotherapy by suppressing tumour relapse and promoting antitumour immune responses.