An indolizine squaraine-based water-soluble NIR dye for fluorescence imaging of multidrug-resistant bacteria and antibacterial/antibiofilm activity using the photothermal effect.

The majority of nosocomial infections are caused by bacteria with antimicrobial resistance and the formation of biofilms, such as implant-related bacterial infections and sepsis. There is an urgent need to develop new strategies for early-stage screening, destruction of multidrug-resistant bacteria, and efficient inhibition of biofilms. Organic dyes that absorb and emit in the near-infrared (NIR) region are potentially non-invasive, high-resolution, and rapid biological imaging materials. In this study, a non-toxic and biocompatible indolizine squaraine dye with water-solubilizing sulfonate groups (SOSQ) is studied for bacterial imaging and photothermal therapy (PTT). PTT is efficient in eliminating microorganisms through local hyperthermia without the risk of developing drug-resistant bacteria. The optical properties of SOSQ are studied extensively in phosphate-buffered saline (PBS). UV-Vis-NIR absorption spectra analysis shows a strong absorption between 650 nm - 1000 nm. SOSQ allows for the wash-free fluorescence imaging of drug-resistant bacteria via NIR fluorescence imaging due to a "turn-on" fluorescence property of the dye when interacting with bacteria. Although SOSQ exhibits no toxicity against both Gram-positive bacteria and Gram-negative bacteria, the PTT property of SOSQ is efficient in killing bacteria as well as inhibiting and eradicating biofilms. PTT experiments demonstrate that SOSQ reduces 90% of cell viability in bacterial strains under NIR radiation with a minimum inhibition concentration (MIC) of >450 μg/mL. The PTT property of SOSQ can also inhibit biofilms (BIC = 1000-2000 μg/mL) and eradicate both preformed young and mature biofilms (MBEC = 1500-2000 μg/mL) as observed by crystal violet assays.