Synthesis and characterization of bevacizumab-functionalized nanoliposomes loaded with regorafenib and fluorescent carbon dots for triple-negative breast cancer theranostics

Abstract

A novel theranostic nanoplatform was developed by a facile and green approach for targeted drug delivery and high-quality fluorescence imaging of triple-negative breast cancer cells (TNBCs). Innovatively synthesized fluorescent carbon dots (CDs) obtained by a hydrothermal method with a zeta potential of −18.4 mV had uniform sizes of <20 nm and high fluorescence quantum yield of 27.3% at 460 nm. Nanoliposomes (NLPs) were synthesized by a thin-film hydration method and loaded with CDs and regorafenib (CR-NLPs) and covalently functionalized with the bevacizumab antibody (BCR-NLPs) by the EDC–NHS method. Monodispersed and high colloidal BCR-NLPs showed a semi-spherical shape in the size range of 100–200 nm and zeta potential of −44.3 mV. HPLC of regorafenib revealed a maximum loading efficiency of 82% and sustained release of 96.4% during 120 h with the first-order kinetic model. The in vitro MTT assay showed the high biocompatibility of CDs, NLPs, CR-NLPs, and BCR-NLPs after 48 h exposure to human fibroblast cells at 200 µg mL⁻¹, with cell viability of 91.4 ± 1.7, 92.2 ± 2.4, 91.5 ± 3, and 88.7 ± 3.1%, respectively. Under the same conditions, potent and specific anticancer activity was observed on MDA-MB-231 cells for CR-NLPs and BCR-NLPs with cell viability of 64.5 ± 1.7 and 47.6 ± 2.3%, respectively. The high-quality fluorescence imaging of MDA-MB-231 cancer cells was also obtained in vitro using BCR-NLPs. The overall results confirmed the high potential of BCR-NLPs for cancer theranostic application.