A mitochondrion-targeted BODIPY-Ir(iii) conjugate as a photoinduced ROS generator for the oxidative destruction of triple-negative breast cancer cells

Abstract

Photodynamic therapy (PDT) provides an alternative option to root out localized triple-negative breast cancer (TNBC) and has been experiencing a surge of research interest over recent years. In this study, we put forward a paradigm of designing novel transition metal-based PSs with the following characteristics: favorable cell-permeability, significant light-harvesting ability and prominent ROS yield. A novel BODIPY-Ir(III) conjugate has been designed as a photoinduced ROS (¹O₂, ˙OH and ˙O₂⁻) generator. BODIPY-Ir is highly photoactive in subduing cancer cells in the PDT regimen with PI values ranging from 172 to 519 and EC₅₀ in the nanomolar regime. Among various cancerous cell lines, TNBC was especially sensitive to BODIPY-Ir-mediated PDT, with a stunning EC₅₀ value of 4.32 nM (PI = 519) under a moderate flux of visible-light irradiation (500 nm, 10.5 mW cm⁻²). BODIPY-Ir mainly accumulates in mitochondria and induces cell apoptosis under irradiation. Furthermore, the nanomolar antiproliferative activity of BODIPY-Ir is retained under hypoxia (2.5% O₂). This work sheds light on instilling the O₂-independent type I mechanism and conferring a red-shift absorption to metal-based PSs which fundamentally facilitate the clinical translation of PSs.