Quadruple functionalized copper-polydopamine nanoparticles for tumor-specific multimodal enhancing photodynamic therapy with low skin phototoxicity

The photoactivity quenching and recovering efficiency are essential for effective stimulation-activated photodynamic therapies (PDT). To maximum the interactions between quencher and photosensitizer in silent state and to scavenge quenchers in active state, a simple GSH-responsive PDT nanomedicine is designed as chlorin e6 (Ce6) loading arginine-copper-polydopamine coordination nanoparticles (Ce6-ACuPDA), which show quadruple functions attributed to the redox-responsive binding and quenching abilities of copper. The photosensitivity of Ce6 is dually quenched directly by the drug-loading substrate and recovers in cancer cells due to the GSH-triggered collapsing of Cu-PDA networks and the reduction of quenchers (Cu(II)). Meanwhile, the Cu(II) oxidates GSH to weaken the cancerous redox barrier and elevates the ultimate efficacy of PDT, which endows the nanomedicine with superior anti-cancer efficacies and low skin phototoxicities. This designing principle focusing on deeply exploiting all functionalities of fewer components provides a facile but effective solution for cancer treatments, demonstrating great therapeutic and industrial potentials.