PhotoPhage: A Virus-based Photothermal Therapeutic Agent

ABSTRACT: Virus-like particles (VLPs) are multifunctional nanocarriers with the pathogenic-like architecture of viruses. They can serve as a safe platform for specific functionalization and immunization, which provides benefits in a wide range of biomedical applications. In this work, a new generation immunophotothermal agent is developed that adjuvants the photothermal ablation using a chemically modified VLP called bacteriophage Qβ. The design is based on the conjugation of near-infrared absorbing croconium dyes to lysine residues located on the surface of Qβ, which turns it to a powerful NIR-absorber called PhotoPhage. This system can generate more heat upon 808 nm NIR laser radiation than free dye with a photothermal efficiency comparable to gold nanostructures yet is biodegradable and acts as an immunoadjuvant combined with the heat it produces. The synergistic combination of thermal ablation with the mild immunogenicity of the VLP leads to effective suppression of primary tumors, reduced lung metastasis, and increased survival time.