Dual-lock-and-key virus-mimicking nanoprobes for ultra-high accurate and sensitive imaging of viral infections in vivo

Fluorescence in situ imaging of viral infection lesions in vivo is crucial for precise diagnosis of viral diseases and evaluation of the extent of viral infection. Nevertheless, achieving highly specific and sensitive fluorescence imaging of viral infection sites in vivo has posed a persistent challenge. Here, we developed a dual-lock-and-key virus-mimicking nanoprobe that consisted of polyamide dendrimers (PAMAM) loaded internally with molecular beacons double-triggered by apurinic/apyrimidinic nucleic acid endonuclease 1 (APE1) and viral RNA (vRNA), and surface-modified with the E protein of Japanese encephalitis virus (JEV). This activatable nanoprobe generated dramatically amplified fluorescent signals stimulated by expressed vRNA and APE1 during viral infection, enabling ultrahigh specific and sensitive imaging of the lesions of JEV infection in vivo. This study provides a potential approach for accurate and sensitive detection of viral infection levels and assessment of the efficacy of antiviral drugs in vivo.