Ofloxacin loaded M0S2 nanoflakes for synergistic mild-temperature photothermal/antibiotic therapy with reduced drug resistance of bacteria

Antibiotic resistance is an increasingly serious threat to global public health, which can lead to the decrease of the effectiveness ofantibiotics. The combination therapy of antibiotic and mild temperature photothermal therapy (PTT) is adopted to address this issue inthis work. An antibiotic-loaded nanoplatform is fabricated based on two-dimensional (2D) molybdenum disulfide (M0S2) nanoflakesas effective near-infrared (NIR) photothermal agent. The M0S2 nanoflakes is modified with positively charged quaternized chitosan(QCS) to improve the dispersion stability and enhance the interaction between M0S2 nanoflakes and bacterial membrane. TheQCS modified M0S2 nanoflakes (QCS-M0S2) is expected to adhere onto the membrane of methicillin-resistant Staphylococcusaureus (MRSA) and depolarize the bacterial membrane by local hyperthermia under NIR irradiation. A first-line antibiotic, ofloxacin(OFLX), can be loaded onto QCS-M0S2 by π-π stacking and hydrophobic interaction. Due to the combined antibiotic-photothermaltherapy, superior bactericidal ability was achieved at mild temperature (45℃) and low antibiotic concentration. Such synergisticmild-temperature photothermal/antibiotic therapy can not only avoid the damage to neighboring tissue by PTT, but also reduce thedevelopment of drug resistance, providing an innovative way for the treatment of bacterial infections.