Cell：突破血脑屏障！张明君/王伊龙团队利用纳米颗粒“劫持”颅骨免疫细胞，让药物直达大脑，已开展人体临床试验

Core Viewpoint - The article discusses a groundbreaking method for drug delivery to the central nervous system (CNS) by utilizing calvarial immune cells to bypass the blood-brain barrier (BBB), which has significant implications for treating CNS diseases [4][5][15]. Group 1: Blood-Brain Barrier and Drug Delivery Challenges - The blood-brain barrier (BBB) is crucial for preventing harmful substances from entering the brain but also limits the delivery of most small and large molecule drugs, hindering treatment for CNS diseases [2][7]. - The high failure rate of clinical trials for CNS drugs is primarily due to the inability of most drugs to cross the BBB, leading to insufficient drug accumulation in the brain and poor therapeutic outcomes [7][8]. Group 2: Innovative Drug Delivery Method - A research team from Tsinghua University and Beijing Tiantan Hospital published a study in Cell, demonstrating that drug-loaded nanoparticles can "hijack" calvarial immune cells to deliver drugs to the CNS by utilizing the skull-meninges channel (SMC) to bypass the BBB [4][10]. - The study confirmed that this method significantly improved short-term and long-term outcomes in preclinical stroke models [4][5]. Group 3: Clinical Trial and Safety - A prospective clinical trial (SOLUTION, NCT05849805) was conducted to assess the safety and feasibility of this method in patients with malignant middle cerebral artery infarction (mMCAI), showing that the intracranial injection procedure is simple and does not cause severe complications [13][15]. - The real-world data from this trial highlights the potential for clinical translation of this innovative drug delivery strategy [13][15]. Group 4: Mechanism and Efficacy - The study utilized albumin nanoparticles that exhibit a tendency to be internalized by immune cells, which then migrate to the CNS injury sites, significantly accumulating in neurons at the damaged areas [12]. - The treatment with drug-loaded nanoparticles demonstrated superior efficacy in reducing ischemic infarction and brain edema compared to conventional methods, achieving these effects with only 1/15 of the usual dosage [12].