Bufotalin-loaded biomimetic prussian blue nanoparticles for colorectal cancer chemo-photothermal therapy via induce ferroptosis

Abstract

Background: As a ferroptosis-inducing platform, based on its release of iron and ferrous ions to induce production of reactive oxygen species (ROS), it has attracted extensive attention in cancer treatment. Since iron-based nanomaterials such as prussian blue (PB), can only produce limited ROS. Bufotalin (CS-5), a promising ferroptosis inducer, was introduced to improve the efficiency of ferroptosis. However, the clinical application of CS-5 was limited by cardiotoxicity and high renal clearance rate. Therefore, we constructed a biomimetic nanosystem (PB@CS-5@M) with satisfactory tumor enrichment ability and long blood circulation time for the treatment of colorectal cancer induced by ferroptosis. Results: In this work, the PB@CS-5@M has efficient loading of CS-5, which significantly reduces the cardiotoxicity of CS-5. After photothermal therapy, the high temperature caused by laser stimulation triggers the release of CS-5, iron and ferrous ions to kill colorectal cancer cells. Furthermore, the ability of CS-5 to significantly down-regulate the expression of GPX4 and HIF-1a, induce ROS production and damage mitochondria to induce ferroptosis in colorectal cancer was amplified. In addition, the down-regulation of HSP70 expression under laser stimulation effectively improved the chemosensitivity of HCT116 cells to CS-5. Conclusions: The chemotherapeutic effect of CS-5 combined with the photothermal effect of PB can effectively treat colon cancer by inducing ferroptosis.