A Hyaluronidase-Responsive Nanoplatform for Near-Infrared Fluorescence Imaging and Synergistic Photodynamic/Gas/Chemodynamic Therapy in Bacterial Infection Sites

Bacterial infections are a serious threat to life and health safety due to their high morbidity and mortality. Currently, the commonly used antimicrobial method is the use of antibiotics, but it is prone to drug resistance. Here, we designed and constructed a nanoplatform F-CLs@HA capable of fluorescent imaging localization at the site of bacterial infection as well as synergizing the three antimicrobial therapeutic methods of photodynamic therapy/gas therapy/chemodynamic therapy (PDT/GT/CDT). It is made by combining carbon dots (CDs) with l-arginine (CL-s) and encapsulated by hyaluronic acid (HA) together with Fe₃O₄. HA is able to target the CD44 receptor, which is overexpressed on inflammatory macrophages, and the higher level of hyaluronidase at the location of bacterial infection is able to hydrolyze HA, releasing antibacterial drugs. CDs are made by the high-temperature reaction of the near-infrared (NIR) dye cyanine 7 (Cy-7), which not only has a PDT effect but also improves the problem of aggregation quenching of small-molecule fluorescent dyes and realizes stable NIR fluorescence imaging. Moreover, Fe₃O₄ is able to release hydroxyl radicals (•OH) as a commonly used drug in CDT. In addition, nitric oxide (NO) released from l-arginine is highly reactive with reactive oxygen species (ROS), generating more toxic reactive nitrogen species (RNS) that induce bacterial death. Both in vivo and in vitro evaluations show that our nanoplatform has favorable imaging and therapeutic effects. In summary, F-CLs@HA has great potential for application in the treatment of bacterial infections.