Naturally-Derived PHA-L Protein Nanoparticle as a Radioprotector Through Activation of Toll-Like Receptor 5

: High energy ray in medical diagnosis and therapy can benefit to patients, but can also cause the significant damages to biomolecules such as DNA, as well as free radical generation, inevitably leading to numerous side effects. Small molecular radioprotectors provide an effective route to preserve the healthy tissue and whole body from ionizing radiation, but always have a short circulation time in body. Inorganic nanoparticles show major protection effect but their heavy metal components considerably jeopardize translational promise due to suboptimal biocompatibility. Herein, we report a novel protein nanoparticle that can overcome limitations of both small molecular and inorganic nanoparticle radioprotectors and can be used as a radioprotector with spontaneous biocompatibility, outstanding pharmacokinetics and improvement on survival rate under exposure to γ-ray irradiation. PHA-L protein nanoparticle serves to clear excessive reactive oxygen species in vivo, prevents radiation-induced hematopoietic and gastrointestinal damages and boosts the survival rate of irradiated mice to ∼70%. A detailed study of the mechanism shows PHA-L protein nanoparticle can target and activate the toll-like receptor 5 in vitro and in vivo, and thus protect irradiated cells by immune response. Importantly, the PHA-L protein nanoparticle can perform highly efficient clearance while eliciting negligible toxicological response.