PhotoPhage: A Virus-based Photothermal Therapeutic Agent

ABSTRACT: Virus like particles (VLPs) are non-infectious multifunctional nanocarriers with the pathogenic-like architecture of viruses. They can serve as a safe platform for precise functionalization and immunization, which provides benefits in a wide range of biomedical applications. In this work, we describe the development of novel immunophotothermal agent for combinatorial photothermal ablation and immunotherapy based on VLP of bacteriophage Qβ. The design was based on covalent conjugation of 212 water soluble near-infrared absorbing croconium dyes to lysine residues located on the surface of Qβ, which turned it to a powerful NIR-absorber with photothermal efficiencies exceeding that of gold nanostructures. This PhotoPhage system generates heat upon 808 nm NIR laser radiation and causes significant cellular cytotoxicity that prevents the progression of primary tumors in mice. It is found that PhotoPhage not only acts as a PTT agent that initiates anti-tumor immune response, but also simultaneously acts as an immunoadjuvant that promotes maturation of dendritic cells, triggers T lymphocyte cells (CD4+, CD8+) and reduces suppressive T regulatory cells leading to effective suppression of primary tumors, reducing lung metastases, and increasing survival time.