Blocking Autophagic Flux Enhances Iron Oxide Nanoparticle Photothermal Therapeutic Efficiency in Cancer Treatment.

Abstract

Autophagy is a conservative eukaryotic pathway which plays a crucial role in maintaining cellular homeostasis, and dysfunction of autophagy is usually associated with pathological conditions. Recently, emerging reports have stressed that various types of nanomaterials and therapeutic approaches interfere with cellular autophagy process, which has brought up concerns to their future biomedical applications. Here, we present a study elaborating the relationships between autophagy and iron oxide nanoparticle (IONP)-mediated photothermal therapy in cancer treatment. Our results reveal that IONP photothermal effect could lead to autophagy induction in cancerous MCF-7 cells in a laser dose-dependent manner, and theinhibition of autophagy would enhance the photothermal cell killing by increasing cell apoptosis. In an MCF-7 xenograft model, cotreatment of autophagy inhibitor and IONP under laser exposure could promote the tumor inhibition rate from 43.26 to 68.56%, and the tumor immunohistochemistry assay of microtubule-associated protein 1-light chain 3 (LC3) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling also demonstrate augmentation in both autophagosomes accumulation and apoptosis in vivo. This work helps us to better understand the regulation of autophagy during IONP-mediated photothermal therapy and provides us with a potential combination therapeutic approach of autophagy modulators and photothermal agents.