pH-responsive cancer-targeted selenium nanoparticles: a transformable drug carrier with enhanced theranostic effects

Abstract

Selenium nanoparticles (SeNPs) have been widely used in various biomedical applications, including cancer therapy, diagnosis and drug delivery. Herein, we fabricated a novel type of structure-transformable capsules by decoration of SeNPs with folate-chitosan to form smart-shell nanocapsules (FAC@CurP–SeNPs). The shrink particles could target cancer cells over expressing folate receptor and enter the cells via folate receptor-mediated endocytosis. FAC@CurP–SeNPs were expanded to snowflake particles under acidifying stimulus (pH 5.3), which led to enhanced drug-release over prolonged periods. Treatment with FAC@CurP–SeNPs significantly inhibited the growth of MCF-7 human breast carcinoma cells through induction of apoptosis, which was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. The contribution of extrinsic and intrinsic apoptotic pathways to the cell apoptosis was confirmed by activation of caspase-9 and caspase-8. Internalized FAC@CurP–SeNPs triggers intracellular ROS overproduction, thus activates p53, MAPKs pathways and inhibits NFκB and to promote cell apoptosis. Our results suggest that FAC@CurP–SeNPs may be a candidate for further evaluation as a agent for human cancers, and the strategy to use transformable nanocapsules could be a highly efficient way to enhance controlled drug release and anticancer efficacy.