Precise construction of Regorafenib-loaded gold nanoparticles: investigation of antiproliferative activity and apoptosis induction in liver cancer cells

Regorafenib (Reg) inhibits the growth of liver cancer cells in vitro and animal model. However, due to its poor bioavailability, its potential as a chemopreventive or therapeutic drug is severely restricted. In this work, we developed two environmentally friendly delivery systems by synthesizing Regorafenib-gold nanoparticles conjugates Reg@GNPs1 and Reg@GNPs2, employing a dual role of Reg to reduce Au3+ and stabilize the synthesized GNPs. UV-Vis’s spectroscopy, Fourier transform infrared spectroscopy, and Powder-XRD verified the fabrication of Reg@GNPs. Reg@GNPs1 and Reg@GNPs2 were both found to be spherical and uniform in size (10 ± 2 and 2 ± 33 nm, respectively) using transmission electron microscopy. Similar negative zeta potential (−35.0 ± 2.5 and −37.0 ± 1.6 mV) was observed by dynamic light scattering analysis, even though the hydrodynamic diameter of the nanoconjugates ranged from 65.0 ± 1.7 to 153.0 ± 2.2 nm. Reg@GNPs1 and Reg@GNPs2 were calculated to have a Reg loading of 46% and 48%, respectively. Selectivity towards the non-cancerous cell line (L929) cells, whereas the MTT assay in vitro showed the antiproliferative effects of Reg@GNPs on three liver carcinoma (Hep3B, BEL7402, and HepG2) cell lines. Several fluorescent staining techniques were used to examine liver cancer cell morphology. Flow cytometric analysis confirmed that the effects of the superior Reg@GNPs nanoconjugate on cell proliferation than free Reg. In conclusion, the acquired results show that the novel synthesized GNPs loaded with Reg are stable as an anticancer agent, with minimal toxicity against non-cancerous cells, as determined by cytotoxicity and IC50 evaluations.