Cationic cyclometalated platinum (II) complexes of metformin with self-assembly and AIE behavior as nuclear and mitochondrial targeted anticancer theragnostic agents

Abstract

Self-assembly and AIE (Aggregation-induced emission) of cyclometalated platinum (II) complexes have attracted lots of attention. The high hydrophilia and low permeability of metformin (Met) has greatly hindered its further clinical application, herein, our work rationally designed and synthesized a pair of theragnostic cyclometalated platinum (II) - metformin complexes. Pt1 and Pt2 can improve bioactivity of Met significantly, and AIE deep-red emission can be mediated by tuning chemical structure of auxiliary ligand in compounds. Moreover, self-assembly of two Pt (II) complexes was revealed, as well as mitochondria and nuclear targeting ability of Pt2 were newly obtained during an AIE process. Meanwhile, Pt2 exhibits 186- and 53-fold enhanced antiproliferative activity compared with Met and Met-free complex analogue, their anticancer mechanisms were also investigated. Herein, our work provides a novel strategy for designing multi-functional platinum-based anticancer theragnostic agents.