Folate-functionalized human serum albumin carrier for anticancer copper(II) complexes derived from natural plumbagin

The folate (FA)-functionalized human serum albumin (HSA) carrier (FA-HSA) is promising for improving the target and efficiency of anticancer drugs. To develop FA-HSA carrier for metal anticancer drugs, we investigated anticancer properties and mechanism of FA-HSA carrier for Cu(II) complexes derived from plumbagin. The fluorescence spectroscopy and molecular docking revealed that Cu(II) complexes bind to IIA subdomain of HSA. Compared with Cu(II) complex alone, FA-HSA-metallodrug complex enhances cytotoxicity to FA-positive cancer cells (HeLa) but do not raise cytotoxicity levels in normal cells in vitro through selectively accumulating in cancer cells to some extent; FA-HSA-metallodrug complex has a stronger capacity for cell cycle arrest in the G2/M phase of HeLa cells, and down-regulating the expression of cyclin-dependent kinase 1 (CDK1) and cyclin B1. Moreover, FA-HSA-metallodrug complex promotes HeLa cells apoptosis through intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway, accompanied by the regulation of Bcl-2 family proteins.