Ca2+ enhanced photosensitizer/DNase I nanocomposite mediated bacterial eradication through biofilm disruption and photothermal therapy

Biofilms are currently responsible for 80 being composed of bacterial communities within self-produced extracellular polymeric substances (EPS) that can resist various adverse factors in the bacterial microenvironment. Therefore, the development of powerful antibacterial systems by disrupting biofilms first and killing exposed free-living bacteria is the top priority for clinical antibiotic needs. In this study, we developed a pH- and photothermally responsive photosensitizer/enzyme-loaded nanocomposite for enhanced biofilm disruption and bacteria killing (gram-positive and gram negative). To achieve this, IR780 (I) as an efficient NIR dye was encapsulated inside the hydrophobic core of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycerol)-2000] (DSPE-PEG2000) micelles (M) for enhanced photothermal therapy. EPS extracellular DNA lyase deoxyribonuclease I (DNase I) was anchored on the micellar surface by calcium phosphate mineralization method. The results indicated that pH-sensitive MI@CaPD nanocomposite degraded as a response to the acidic conditions characteristic for the bacterial environment and released DNase I and Ca2+ ions simultaneously. Subsequently, the Ca2+ stabilized the DNase I active structure and facilitated the dispersion of the biofilm EPS. Then, interior bacteria were exposed and killed by IR780-mediated hyperthermia. The synergistic effect of DNase I and photothermal therapy could efficiently eradicate the biofilms, which exhibits superior biofilm dispersion and destruction capability.