Carboxymethyl Chitosan-Based Polyselenolipoic Acid Nanoparticle against a Bacterial Liver Abscess by a Dual-Barrier Disruption Strategy

The abscess wall and biofilm of a bacterial liver abscess (BLA) are two major barriers that inhibit immune clearance and antimicrobial treatment, leading to issues such as prolonged treatment cycles and poor prognosis. In this study, we propose a dual-barrier disruption strategy employing a pH-driven charge-reversal nanoparticle (PSeLA@CMCS) to disrupt biofilms and the abscess wall. PSeLA@CMCS carries a positive charge in the acidic abscess cavity, penetrates biofilms, and releases dihydroselenolipoic acid (DHSeLA) in response to glutathione. Sequentially, DHSeLA inhibits bacterial proliferation by interfering with bacterial metabolism, disrupts the biofilm by cleaving eDNA, and damages the abscess wall by breaking the disulfide bonds of fibrin(ogen). Ultimately, macrophages enter the abscess cavity and eliminate bacteria through phagocytosis. This dual-barrier disruption strategy achieves effective treatment of BLA and significantly improves its prognosis. Furthermore, this study provides an approach for the treatment of BLA and other visceral abscesses.