Cyclic Mitochondria-penetrating Peptides with Histidin-Ir(III) Coordination as Mitochondria-targeted Theranostic and Photodynamic Anticancer

Abstract

Mitochondria-targeted anticancer drugs act through directly disrupting the energy producing systems of cancer cell mitochondria, producing reactive oxygen species (ROS) and activating mitochondrial-dependent cell death signaling pathways. Based on the fact that most mitochondrial damage can lead to apoptosis, it has been proven that photodynamic therapy targeting mitochondria is a very effective strategy. Recently, cyclometalated Iridium(III) complexes have gained increasing attention in bioimaging and biosensing due to their rich photophysical properties. e.g., large Stokes shifts, good biocompatibility, and high photostability. In this present work, We have synthesized mitochondria penetrating peptide with histidin on both ends: HK(Fxr)n-H. These Histidin side group is utilized for the formation of complex with Ir(III) and hence generate cyclic peptide with mitochondria penetrating property. The ring size has been varied by changing the number of amino acid sequence to find the optimum ring size for better penetration. Ir(III) complexes can function as efficient photosensitizers (PSs) for producing singlet oxygen (1O2). Due to the easy modification of the ligands, the photophysical and biological properties of Ir(III) complexes can be readily tuned. So this peptide can induce rapid cell death upon photo irradiation and can serve as a novel photodynamic therapeutic agent for cancer therapy. Moreover, most of the mitochondria targeting agent failed to deliver high molecular weight cargo to mitochondria. So our molecular design can be a solution problem as it can carry high molecular weight cargo by conjugation to it.