Molecular engineering of covalent organic frameworks with elevated mitochondrial-targeting for cancer cell suppression

Covalent organic frameworks (COFs) have appeared as a variety of promising nanomaterials for photodynamic therapy (PDT) owing to their excellent biosafety and structural diversity. However, finite aqueous dispersibility, deficient subcellular targeting ability and undesirable PDT efficiency had seriously restricted their biomedical application. Herein, we prepared two solution-dispersible nanoparticle COFs via a mild solution-phase synthesis, denoted as EB-TFP and DPP-TFP, investigating the effect of COF’s surface charges on their subcellular targeting ability and PDT efficiency. With tuning the COF’s surface charges, the positive charged COFs (EB-TFP) possessed the elevated mitochondrial targeting ability, higher O2-. generation ability and fluorescence at 510 nm. Therefore, EB-TFP successfully employed as multifunctional PSs with excellent mitochondrial targeting ability for the imaging-guided type Ⅰ PDT. This work provides a “killing two birds with one stone” strategy to improve subcellular targeting and ROS generation ability for expanding the biomedical applications via tuning the COFs’ surface charges.