Synthesis Of Ruthenium (?) Complexes And Their Applications In Chemotherapy And Phototherapy

In recent years,ruthenium(?)complexes have been widely developed and studied in photodynamic therapy and chemotherapy due to their abundant photophysical and photochemical activities and excellent biological properties.Currently,four ruthenium anti-tumor complexes are in clinical trials.Based on the two common structures of ruthenium(?)complexes(polypyridine ruthenium(?)complexes and arene ruthenium(?)complexes),in this paper,two series of ruthenium(?)complexes are designed and synthesized based on rational design of functional ligands.The in vitro anti-tumor antivities and underlying mechanisms were explored at the cellular level.The main contents of this paper are as follows:(1)A novel ruthenium(?)-based photosensitizer(Ru-BDP)was designed and synthesized through the coordination of boron dipyrromethene dyes(BDP)to polypyridine ruthenium(?).Ru-BDP was further co-assembled with dual hydrophilic block copolymer polyoxyethylene-b-polyacrylic acid(PEO-b-PAA)to form nanomicelle Ru-BDP-NPs.The experimental results show that the prepared nanomicelles are uniform with an average size of about 157 nm.After entering tumor cells,Ru-BDP-NPs could undergo ligand dissociation under the irradiation of green light(540 nm,0.4 W/cm~2),resulting in the increase of the fluorescence intensity.Meanwhile,the singlet oxygen produced by polypyridine ruthenium(?)can induce tumor cell death which achieves the goal of integration of diagnosis and treatment.(2)Three arene ruthenium(?)anti-tumor complexes were synthesized by tethering the glutathione transferase(GSTs)inhibitor NBDHEX to arene ruthenium(?)complexes.The in vitro experiment shows that the prepared ruthenium(?)complexes exhibited considerable anti-proliferative activity against the tested cancer cells,especially 3-7,which showed higher activity and selectivity than cisplatin.