Photo-controllable burst generation of peroxynitrite based on synergistic interactions of polymeric nitric oxide donors and IR780 for enhancing broad-spectrum antibacterial therapy

The newly attractive peroxynitrite (ONOO-) therapy can prominently enhance antibacterial therapeutic efficacy. However, it is a great challenge but urgently needed to generate ONOO- with adjustable release rate and dosage in order to satisfy personalized treatments for different disease types and severities. Herein, PSNO@IR780 nanoparticles are fabricated via co-assembly of an amphiphilic PEG-b-PAASNO block copolymer grafted with abundant nitric oxide (NO) donor units and IR780 as a photothermal and photodynamic agent. Photo-controllable burst generation of ONOO- from PSNO@IR780 nanoparticles could be realized based on synergistic reactions of rapid NO release induced by increased local temperature and efficiently produced superoxide anion radical (O2•-) from IR780. The maximum ONOO- release dosage is up to 6.73 ± 0.07 µM and release rate is up to 98.1 ± 1.38 nM/s. Furthermore, the ONOO- release behavior can be precisely manipulated by varying sample concentrations, irradiated durations, output power densities, and laser switches, respectively. Ultra-efficiently generated ONOO- from biocompatible PSNO@IR780 nanoparticles significantly elevated broad spectrum antibacterial efficiency through damaging bacterial membranes. Thus, PSNO@IR780 nanoparticles may present a new insight into preparation of burst and controllable generating ONOO- materials, and provide new opportunities for antibacterial therapy. STATEMENT OF SIGNIFICANCE: 1. Polymeric NO donor (PEG-b-PAASNO) grafted with abundant NO donor units was synthesized. 2. PSNO@IR780 nanoparticles were prepared by co-assembly of IR780 and amphiphilic PEG-b-PAASNOpolymer. 3. The maximum ONOO- release dosage from PSNO@IR780 nanoparticles was 6.73 ± 0.08 µM. 4. The fastest ONOO- release rate from PSNO@IR780 nanoparticles was 98.1 ± 1.4 nM/s. 5. Ultra-efficiently generated ONOO- significantly elevated antibacterial efficiency via damaging bac-terial membranes.