Zhao Mei, Lin Yuanyuan, Zeng Yuteng, Lv Ziyan, Liang Jiayu, Tang Puxian, Zhen Xuechu, Han Liang
Jiangsu Key Laboratory of Neuropsychiatric Diseases Research, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Jiangsu Key Laboratory of Neuropsychiatric Diseases Research, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Soochow University, Suzhou 215123, China.
J Control Release. 2025 Feb 10;378:763-775. doi: 10.1016/j.jconrel.2024.12.066. Epub 2024 Dec 29.
Many brain-targeting drug delivery strategies have been reported to permeate the blood-brain barrier (BBB) via hijacking receptor-mediated transport. However, these receptor-based strategies could mediate whole-brain BBB crossing due to the wide intracranial expression of target receptors and lead to unwanted accumulation and side effects on healthy brain tissues. Inspired by brain metastatic processes and the selectivity of brain metastatic cancer cells for the inflammatory BBB, a biomimetic nanoparticle was developed by coating drug-loaded core with the inflammatory BBB-seeking erythrocyte-brain metastatic hybrid membrane, which can resist homotypic aggregation and specially bind and permeate the inflammatory BBB for specific drug delivery. Dexamethasone and embelin were used as model drugs to be loaded in the biomimetic nanoparticles to restore plasmin-mediated attacks against brain metastases. The drug-loaded nanoparticles were proved to inhibit tumor serpin secretion to restore local plasmin production, which could inactivate tumor cell surface L1CAM to inhibit vessel-spreading-dependent tumor growth and produce lethal soluble factor-related apoptosis ligands (sFasL) to induce tumor cell apoptosis, leading to the suppression of the intracranial metastatic nodule development and prolonged survival of mice with brain metastases. The inflammatory BBB-seeking biomimetic approach represents an effective regimen for potent therapy against brain metastases.
据报道，许多脑靶向给药策略通过劫持受体介导的转运来穿透血脑屏障（BBB）。然而，由于靶受体在颅内广泛表达，这些基于受体的策略可能介导全脑BBB穿越，并导致在健康脑组织中出现不必要的蓄积和副作用。受脑转移过程以及脑转移癌细胞对炎症性血脑屏障的选择性启发，通过用寻求炎症性血脑屏障的红细胞-脑转移杂交膜包裹载药核心，开发了一种仿生纳米颗粒，该纳米颗粒可以抵抗同型聚集，并特异性结合和穿透炎症性血脑屏障以进行特定的药物递送。地塞米松和紫铆因被用作模型药物加载到仿生纳米颗粒中，以恢复纤溶酶介导的对脑转移的攻击。载药纳米颗粒被证明可以抑制肿瘤丝氨酸蛋白酶抑制剂的分泌，以恢复局部纤溶酶的产生，这可以使肿瘤细胞表面的L1细胞粘附分子失活，从而抑制依赖血管扩散的肿瘤生长，并产生致死性可溶性因子相关凋亡配体（sFasL）以诱导肿瘤细胞凋亡，从而抑制颅内转移结节的发展并延长脑转移小鼠的生存期。寻求炎症性血脑屏障的仿生方法代表了一种有效的治疗脑转移的方案。
