Cathepsin B-responsive multifunctional peptide conjugated gold nanorods for mitochondrial targeting and precise photothermal cancer therapy

Nanomaterials have shown great potential in cancer therapy, but the phenomenon of poor tumor recognition without cellular organelle accumulation usually leads to reduced therapeutic effects and enhanced side effects. Herein, we resolved this issue by employing a multifunctional peptide coating mainly composed of, from the inside out, a mitochondrial targeting segment, a cathepsin B-responsive segment and a zwitterionic antifouling segment. Then gold nanorods were modified with a peptide via ligand exchange, displaying excellent photothermal property and superior stability both before and after enzyme treatment. The in vitro and in vivo results showed that this nanoplatform possessed good biocompatibility, satisfactory mitochondria targeting ability, prolonged blood circulation lifetime and enhanced cellular uptake in tumors. This nanoplatform promoted effective near-infrared light-triggered subcellular hyperthermia treatment in vitro and exhibited excellent tumor ablation ability in vivo. These findings suggested that this multifunctional nanoplatform could significantly enhance the therapeutic efficiency of photothermal therapy based on activated mitochondrial targeting. CO 2021 Elsevier Inc. All rights reserved.

Automated summary

Using a multifunctional peptide coating on gold nanorods, this study addressed the poor tumor recognition issue in cancer therapy, enhancing therapeutic effects and reducing side effects. In vitro and in vivo results demonstrated the excellent treatment efficacy of the nanoplatform, promoting effective near-infrared light-triggered subcellular hyperthermia therapy.