Amplifying bacterial cuproptosis by NIR driven biomimetic metal organic framework for nanocatalytic enhanced bacterial pneumonia immunotherapy.

Abstract

The clinical therapy of infectious diseases such as bacterial pneumonia poses a major concern for the medical community. Traditional antibiotic therapies can be cytotoxic, and easy to develop bacterial resistance. Herein, we proposed a novel biomimetic nanoplatform called CM consisted of Cu based metal organic framework, and followed by being wrapped by macrophage membrane (MM). <i>In vitro</i> and <i>in vivo</i> results both confirmed that CM inherited the properties of original MM, specifically targeting the infectious site, achieved the near infrared (NIR) mediated Cu ions accumulation inside bacteria, and produced endogenous reactive oxygen species and inflammation related factors, ultimately resulting in the efficient bacteria elimination. In addition, transcriptomics and metabolomics revealed that CM + NIR induced intracellular Cu overload, thereby promoting bacterial cuproptosis. Significantly, CM + NIR roused immunoregulation to eliminate bacteria through inducing macrophage M1 polarization, and adjusting the number and proportion of immune cells. Altogether, CM + NIR promoted bacterial cuproptosis together with immunoactivation for all-stage bacterial elimination, resulting in precise bacterial pneumonia therapy, and also providing a generalized approach for targeted therapy of infectious diseases.