1550 nm light activatable photothermal therapy on multifunctional CuBi2O4 bimetallic particles for treating drug resistance bacteria-infected skin in the NIR-III biological window

Nanomaterial mediated phototherapies are believed to be promising candidates to overcome the bacterial drug resistance crisis. However, due to the lack of nanomaterials able to absorb long NIR light, especially in the NIR-III (1500-1850 nm) and -IV (2100-2300 nm) regimes, it was never investigated the utilization of NIR-III and NIR-IV light for in vivo treatments of cancer or bacterial infections. To this end, plasmonic metal-doped transition metal oxides (TMO) are attracting a great attention due to their tunable surface plasmon resonance absorption to the NIR region. Unique features with extendable NIR light absorption of plasmonic metal-doped transition metal oxides make their applications very attractive in several fields, but their utilization for bacterial infection treatments was not yet reported. Moreover, up-to-date bacterial eradication was limited to phototherapies in the NIR-I (700-950 nm) and NIR-II (1000-1350 nm) biological windows (BWs) and has not yet been studied in the NIR-III (1500-1870 nm) BW. To overcome these literature limitations, we engineered NIR-III (1550 nm) light activatable multifunctional plasmonic CuBi2O4 bimetallic particles (i.e., CBO bMPs) with very high molar extinction coefficients (2.75 × 1011 M-1cm-1 @ 808 nm, 2.75 × 1011 M-1cm-1 @ 980 nm, and 3.5 × 1011 M-1cm-1 @1550 nm), able to absorb and convert long NIR (980 and 1550 nm) light energy to thermal heat and generate cytotoxic reactive oxygen species (ROS) for in vivo treatment of drug resistant bacterial infections. Our in vitro and in vivo results reveal that NIR-III (1550 nm) light irradiation of CBO bMPs exerts a remarkable in vivo antibacterial activity via NIR-III photothermal therapy (NIR-III PTT), which is superior than its corresponding NIR-I (808 nm) PTT and NIR-II photodynamic therapy (NIR-II PDT, 980 nm). We observed that hyperthermia-based photothermal therapy is more effective than ROS-based photodynamic therapy in killing multi-drug resistant bacteria. We also show that CBO bMPs also show an enzyme oxidase and peroxidase like activity, which is an additional asset to enhance the therapeutic efficiency.