Gallbladder cancer progression is reversed by nanomaterial-induced photothermal therapy in combination with chemotherapy and autophagy inhibition

Abstract

Introduction: Gallbladder cancer (GBC) is the most common malignancy in biliary tract with extremely poor prognosis. Photothermal therapy (PTT) shows great promises for tumor therapy, which causes tumor cell death via selectively directed heating released by nanoparticles under the near-infrared irradiation. Through degrading damaged organelles and mis-folded proteins in autophagosomes, autophagy plays a vital role in maintaining the intracellular homeostasis. The present study attempted to combine chemotherapy and autophagy blocking with PTT. Materials and Methods: We purchased multi-walled carbon nanotubes from Nanostructured and Amorphous Materials and performed PTT using an 808-nm diode laser. The cytotoxic effects of PTT and chemotherapy in vitro were assessed by cell viability analysis. The effects of PTT and chemotherapy on autophagy in vitro were assessed by GFP-LC3 and Western blot. And these results were confirmed by in vivo experiment. Results: Both PTT and chemotherapy could trigger cytoprotective autophagy to tolerate the cellular stresses and prolong the survival of GBC cell; therefore, the blocking of autophagy could enhance the efficacy of PTT and chemotherapy in GBC treatment in vitro and in vivo. Conclusion: Chemotherapeutic drug doxorubicin and autophagy inhibitor chloroquine could enhance the efficacy of nanoparticle-mediated hyperthermia in GBC.