Multifunctional Gold Nanoclusters for a Lung Tissue Distribution Study of a Novel Anti-asthma Inhaled Antibody

Pulmonary delivery of monoclonal antibodies has revolutionized the treatment of various types of lung diseases, such as severe asthma. However, the inconsistent antibody drug concentrations in the lungs and serum highlight the importance of monitoring the actual antibody distribution change in the lungs. In this study, we developed a novel antibody-functionalized gold nanocluster with high spatiotemporal resolution for fluorescence/CT dual-modal imaging based on an antibody targeting an allergic-airway-inflammation-related free cytokine in lungs. Specifically, the antiasthmatic effects of an IL-5-specific antibody (reslizumab) were first confirmed following pulmonary administration in mice, and reslizumab-functionalized gold nanoclusters successfully achieved the real-time and in situ monitoring of the therapeutic antibody's change in lung tissues and differentiated the discrepancy between asthmatic and normal mice under fluorescence or CT imaging systems at an early stage after administration. As a proof of concept, it is the first report that an antibody-functionalized gold nanocluster could be used to provide comprehensive pharmacokinetic and pharmacodynamic insight into the quick lung tissue distribution change of a monoclonal antibody drug in mice, which will facilitate the development of both inhaled antibody drugs and other tissue-specific therapeutic antibodies that target different disease-related factors that are pathologically overexpressed in a specific tissue or organ.