Synergistic anticancer therapy via ferroptosis using modified bovine serum albumin nanoparticles loaded with sorafenib and simvastatin

Ferroptosis is a non-apoptotic cell death pathway characterized by the accumulation of lipid-peroxy radicals within the affected cells. Here, we investigate the synergistic capacity of sorafenib (SOR) and simvastatin (SIM) to trigger ferroptosis for cancer therapy. For precise in-vivo delivery, SOR + SIM was ratiometrically loaded in bovine serum albumin nanoparticles (BSA-NPs) modified with 4-carboxy phenylboronic acid (CPBA). The developed CPBA-BSA(SOR + SIM)-NPs revealed size of 175.2 +/- 12.8 nm, with PDI of 0.22 +/- 0.03 and Z-potential of-29.6 +/- 4.8 mV. Significantly, CPBA-BSA(SOR + SIM)-NPs exhibited > 2 and > 5-fold reduction in IC50 values compared to individual SOR and SIM treatments respectively, in all tested cell lines. Moreover, CPBA-BSA(SOR + SIM)-NPs treated cells exhibited decrease in glutathione levels, increase in malonaldehyde levels and depolarization of mitochondrial membrane potential (JC-1 assay). Pharmacokinetic analysis revealed enhanced AUC(0-infinity) and MRT levels for SOR and SIM when administered as CPBA-BSA(SOR + SIM)-NPs compared to free drugs. Crucially, in in-vivo experiments, CPBA-BSA(SOR + SIM)-NPs led to a significant reduction in tumor volume compared to various control groups. Histological and biomarker analyses underscore their biocompat-ibility for clinical applications. In conclusion, this study highlights the potential of CPBA-BSA(SOR + SIM)-NPs as a promising strategy for inducing ferroptosis in cancer cells, concurrently improving drug delivery and thera-peutic efficacy. This approach opens new avenues in cancer treatment.

Automated summary

This study investigates the synergistic effect of sorafenib and simvastatin in triggering ferroptosis for cancer therapy. The researchers developed bovine serum albumin nanoparticles loaded with both drugs and observed a significant reduction in tumor volume in in-vivo experiments. The study highlights the potential of this drug delivery system for inducing ferroptosis and improving therapeutic efficacy.