Cancer-exocytosed exosomes loaded with bio-assembled AgNCs as smart drug carriers for targeted chemotherapy

Abstract

Drug resistance remains one of the major hurdles to the effective cancer therapy. Recently emerged field of nanotechnology holds great promises for effective and target specific conveyance of therapeutic cargo to malignant sites. Exosomes have been recently come into focus as drug carriers as they are nano-sized, biocompatible and can cross blood brain barriers (BBB). Exosomes exocytose from almost every type of cells and can be separated from body fluids or cell culture medium. Herein, we have developed the new bioresponsive self-assembly of drug-delivery platform through the in situ biosynthesized exosomes (D-AgNCs@ExoU87), isolated by ultracentrifugation from the cell culture medium of glioblastoma cells (U87) after incubation with [Ag (GSH)]+ and DOX separately and combined. These engineered exosomes are highly cancer targeting and biocompatible, sphere-shaped with the average size of 30–120 nm, and can be used as early cancer diagnosis. The D-AgNCs@ExoU87 showed higher cellular accumulation as compared to D@ExoU87, suggesting the efficiency of the bio-responsive self-assembled silver nanoclusters (AgNCs) as smart cancer targeting agents. Moreover, the as-prepared D-AgNCs@ExoU87 cause cytotoxicity involved reactive oxygen species (ROS) damage in cancer cells and have no activity on healthy cells. In addition, the higher efficacy of the intelligent drug release under acidic conditions was clearly observed. This raises the possibility to provide the smart drug delivery platform through the bio-responsive self-assembled exosomes loaded with biocompatible fluorescent nanoclusters including AgNCs exocytosed from tumor cells for cancer diagnosis and targeted chemotherapy.