A dual-targeting photosensitizer for simultaneous mitochondrial and lysosomal disruption in cancer and antibacterial photodynamic therapy†

Abstract

Mitochondria and lysosomes are key organelles involved in cell survival and death. Mitochondria regulate energy production, reactive oxygen species (ROS) levels, and apoptosis, while lysosomes manage waste degradation and also play a role in cell death through enzyme release when damaged. Cancer cells often contain more active lysosomal enzymes, making them more vulnerable to lysosome-related cell death. Targeting these organelles with photosensitizers (PSs) in photodynamic therapy (PDT) can achieve enhanced anticancer effects. Dual-targeting PSs, especially those that affect both mitochondria and lysosomes, are rare but highly promising. By simultaneously damaging both organelles, such PSs may trigger stronger therapeutic responses. In this study, we present a novel dual-targeting photosensitizer, MCQ-1, which localizes to both mitochondria and lysosomes and serves as an efficient type I PS for cancer cell treatment. Additionally, MCQ-1 demonstrates remarkable antibacterial activity against Gram-positive bacteria, including Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), under white LED irradiation.