Ofloxacin loaded MoS2 nanoflakes for synergistic mild-temperature photothermal/antibiotic therapy with reduced drug resistance of bacteria

Abstract

Antibiotic resistance is an increasingly serious threat to global public health, which can lead to the decrease of the effectiveness of antibiotics. The combination therapy of antibiotic and mild temperature photothermal therapy (PTT) is adopted to address this issue in this work. An antibiotic-loaded nanoplatform is fabricated based on two-dimensional (2D) molybdenum disulfide (MoS2) nanoflakes as effective near-infrared (NIR) photothermal agent. The MoS2 nanoflakes is modified with positively charged quaternized chitosan (QCS) to improve the dispersion stability and enhance the interaction between MoS2 nanoflakes and bacterial membrane. The QCS modified MoS2 nanoflakes (QCS-MoS2) is expected to adhere onto the membrane of methicillin-resistant Staphylococcus aureus (MRSA) and depolarize the bacterial membrane by local hyperthermia under NIR irradiation. A first-line antibiotic, ofloxacin (OFLX), can be loaded onto QCS-MoS2 by π-π stacking and hydrophobic interaction. Due to the combined antibiotic-photothermal therapy, superior bactericidal ability was achieved at mild temperature (45 °C) and low antibiotic concentration. Such synergistic mild-temperature photothermal/antibiotic therapy can not only avoid the damage to neighboring tissue by PTT, but also reduce the development of drug resistance, providing an innovative way for the treatment of bacterial infections.