Photosensitizer Nanodot Eliciting Immunogenicity for Photo-Immunologic Therapy of Postoperative Methicillin-Resistant Staphylococcus aureus Infection and Secondary Recurrence

The treatment of postoperative infection caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has become an intractable clinical challenge owing to its low therapeutic efficacy and high risk of recurrence. Apart from imperfect antibacterial therapies, induction of insufficient immunogenicity, required for the successful clearance of a pathogen, may also contribute to the problem. Herein, an ultra-micro photosensitizer, AgB nanodots, using photothermal therapy, photodynamic therapy, and Ag⁺ ion sterilization, are utilized to efficiently clear invading MRSA both in vitro and in vivo. AgB nanodots are also found to upregulate host immunogenicity in a murine model and establish immunological memory by promoting the upregulated expression of danger signals that are commonly induced by stress-related responses, including sudden temperature spikes or excess reactive oxygen production. These stimulations boost the antibacterial effects of macrophages, dendritic cells, T cells, or even memory B cells, which is usually defined as infection-related immunogenic cell death. Hence, the proposed AgB nanodot strategy may offer a novel platform for the effective treatment of postoperative infection while providing a systematic immunotherapeutic strategy to combat persistent infections, thereby markedly reducing the incidence of recurrence following recovery from primary infections.