Design of a Novel Drug Delivery Nanosystem that Simultaneously Realizes Real‐Time Tracing and Drug Delivery Across the Blood–Brain Barrier

Abstract Acute encephalitis is a brain infection that can harm the nervous system if not recognized and treated promptly. However, the presence of the blood–brain barrier restricts therapeutic agent distribution from the bloodstream to the brain parenchyma, severely restricting effective therapy for this disease. Herein, a novel drug delivery system based on a macrophage (RAW 264.7 cells) artifactual diagnostic and therapeutic nanoparticles (IPD@RAW) drug‐loading approach is presented, which exploits RAW cells' ability to cross the blood–brain barrier and go toward inflammation, and efficiently realizes the targeted enrichment of diagnostic and therapeutic nanoparticles at the site of inflammation in the brain. This nano‐drug‐carrying technology can accurately depict the degree of inflammation in real time for an extended period due to the significant penetration depth and high signal‐to‐noise ratio of near‐infrared (NIR) imaging. Meanwhile, the modified polydopamine can trigger the controlled release of anti‐inflammatory drugs through photothermal conversion under NIR irradiation to reduce the expression of cellular inflammatory factors, such as TNF‐α, IL‐6, and IL‐1β, and alleviate the brain damage due to secretion of this inflammatory factor. As a result, this drug delivery system provides a reliable tool for overcoming the blood–brain barrier to achieve early diagnosis and treatment of acute encephalitis.