Targeted photothermal therapy of mice and rabbits realized by macrophage-loaded tungsten carbide.

Abstract

Although great advances have been made in photothermal therapy, the efforts hitherto have mainly achieved antitumor effects in mice with a subcutaneous tumor model, which is less clinically relevant. Therefore, it is very urgent to make further progress in investigating the possibility of larger animal models with orthotopically xenografted tumors for further clinical trials. Herein, macrophage-loaded tungsten carbide has been employed for the photothermal ablation of orthotopic breast tumors in rabbits in a targetable way. Tungsten carbide as an excellent photoactive material can induce on-site hyperthermia and even reactive oxygen species for tumor destruction; meanwhile, the macrophage is a biocarrier that behaves as a "Trojan horse" for tumor targeting. Both experimental results and theoretical simulations verified the broadband photoabsorption of WC. The WC loaded in the macrophages readily maintains the photothermal and photodynamic effects of the bare WC, while its accumulation at the tumor site is nearly 10 times that of bare WC. As such, the complete removal of solid tumors in rabbits was confirmed with the aid of B-mode ultrasound and contrast-enhanced ultrasound surveillance. Apparently, this work advances photothermal therapy one step further to large animal models with orthotopic tumors.