Carrier-free nanoassemblies of AIE-sulfonates and DNase-1 with high loading efficiency for digesting NETs and...

While hydrophobic low-molecular-weight photosensitizers can be assembled into nanoparticles through protein-based carriers, their low encapsulation efficiency and non-physiological assembly conditions usually limit the co-assembly of functional enzymes with photosensitizers. To address this, we found aggregation-induced emission (AIE)-based photosensitizers with sulfonic acid groups (named TRS1, TRS2, and TRS3) induced the self-assembly of DNase-1 into nanoparticles (DNase-1/TRS NPs) with high loading efficiency. The assembled nanoparticles maintained ROS generation capacity for tumor cell/tissue elimination, whereas DNase-1 exhibited improved enzymatic activity. Upon activation by specific stimuli, DNase-1 was demonstrated to exhibit robust catalytic function. In vivo studies confirmed that the nanoparticles effectively degraded neutrophil extracellular traps (NETs) in hepatic tissue and suppressed primary tumor growth. Collectively, the DNase I/TRS NPs system provides an innovative strategy for digesting NETs and photodynamic therapy via carrier-free nanoassemblies of AIE-sulfonates and DNase-1.