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 (O) 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.