A potent formula against triple-negative breast cancer-sorafenib-carbon nanotubes-folic acid: Targeting, apoptosis triggering, and bioavailability enhancing.

Abstract

Triple-negative breast cancer (TNBC) has short survival rates. This study aimed to prepare a novel formula of sorafenib, carbon nanotubes (CNTs), and folic acid to be tested as a drug delivery system targeting versus TNBC compared with free sorafenib and to evaluate the formula stability, in vitro pharmacodynamic, and in vivo pharmacokinetic properties. The formula preparation was done by the synthesis of polyethylene glycol bis amine linker, CNT PEGylation, folic acid attachment, and sorafenib loading. The prepared formula has been characterized using X-ray diffraction, Flourier-transform infrared, ¹HNMR, UV, high resolution-transmission electron microscope, field emission scanning electron microscopy, and Zeta potential. In vitro studies included drug release determination, MTT assay, flow cytometry to determine the apoptotic stage with percent, cell cycle analysis, and apoptotic marker assays for caspase-3, 8, 9, cytochrome c, and BCL-2. The in vivo study was performed to determine bioavailability and half-life in rats. The in vitro MTT antiproliferative assay revealed that the formula was threefold more cytotoxic toward TNBC cells than free sorafenib, and the flow cytometry showed a significant increase in apoptosis and necrosis. The formula has a greater inhibitory effect on BCL-2 and a lessening effect on cytochrome c and caspases 3, 8, and 9 than free sorafenib. In vivo experiments proved that our novel formula was superior to free sorafenib by increasing bioavailability by eight times and prolonging the half-life by three times. These results confirmed the successful preparation of the desired formula with better pharmacodynamic and pharmacokinetic properties. These promising results may show a novel therapeutic strategy for TNBC patients.