Molecular engineering based on four-arm perylene diimide chromophores toward hypoxia-induced specific photothermal
Kecheng Huang1, Xiangkun Cui2, Miaomiao Zhen1
1Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China. xyq@bit.edu.cn.
Abstract:
Perylene diimide (PDI) radical anions have attracted increasing attention as hypoxia-responsive photothermal agents due to their strong near-infrared (NIR) absorption and efficient photothermal conversion. However, their biomedical application is often limited by aggregation-induced quenching and poor structural tunability. In this work, we report a rationally engineered four-arm PDI derivative (PDI-4Alky·4Cl) bearing terminal alkyne groups, which not only suppresses π-π stacking via steric and electrostatic repulsion, but also serves as a versatile molecular scaffold for further functionalization. The resulting PEGylated product (PDI-2PEG) exhibits excellent aqueous stability, high radical yield, and strong NIR photothermal performance (conversion efficiency up to 51.6%). Importantly, PDI-2PEG demonstrates hypoxia-triggered radical generation and tumor-specific photothermal ablation in vivo. This study highlights a structurally modular PDI platform that integrates radical-based photothermal therapy with synthetic flexibility, offering a promising strategy for the development of next-generation tumor-selective theranostic agents.
