Focused Ultrasound‐Responsive Nanocomposite with Near‐Infrared II Mechanoluminescence for Spatiotemporally Selective Immune Activation in Lymph Nodes

Abstract The immune regulation of the lymphatic system, especially the lymph node (LN), is of great significance for the treatment of diseases and the inhibition of pathogenic organisms spreading in the body. However, achieving precise spatiotemporal control of immune cell activation in LN in vivo remains a challenge due to tissue depth and off‐target effects. Furthermore, minimally invasive and real‐time feedback methods to monitor the regulation of the immune system in LN are lacking. Here, focused ultrasound responsive immunomodulator loaded nanoplatform (FURIN) with near‐infrared II (NIR‐II) luminescence is designed to achieve spatiotemporally controllable immune activation in LN in vivo . The NIR‐II persistent luminescence of FURIN can track its delivery in LN through bioimaging. Under focused ultrasound (FUS) stimulation, the immunomodulator encapsulated in FURIN can be released locally in the LN to activate immune cells such as dendritic cells and the NIR‐II mechanoluminescence of FURIN provides real‐time optical feedback signals for immune activation. This work points to a FUS mediated, spatiotemporal selective immune activation strategy in vivo with the feedback control of luminescence signals via ultrasound responsive nanocomposite, which is of great significance in improving the efficacy and reducing the side effect of immune regulation for the development of potential immunotherapeutic methods in the future.