Nanoparticles Coated with Brain Microvascular Endothelial Cell Membranes can Target and Cross the Blood–Brain Barrier to Deliver Drugs to Brain Tumors

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2024-07, Vol.20 (29), p.e2306714-n/a
• Main Authors: Chen, Huajian, Ji, Jingsen, Zhang, Li, Luo, Chuangcai, Chen, Taoliang, Zhang, Yuxuan, Ma, Chengcheng, Ke, Yiquan, Wang, Jihui
• Format: Article
• Language: English
• Subjects: Animals; bEnd.3 cell; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Brain - blood supply; Brain - metabolism; brain microvascular endothelial cells; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell membranes; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Delivery Systems; Endocytosis - drug effects; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; glioblastoma; Humans; Mice; Nanoparticles; Nanoparticles - chemistry; Polyethylene glycol; Polyethylene Glycols - chemistry; Tumors
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.202306714

The blood–brain barrier (BBB) contains tightly connected brain microvascular endothelial cells (BMECs) that hinder drug delivery to the brain, which makes brain tumors difficult to treat. Previous studies have shown that nanoparticles coated with tumor cell membranes selectively target their homologous tumors. Therefore, this study investigated whether bEnd.3‐line BMEC membrane‐coated nanoparticles with poly(lactide‐co‐glycolide)‐poly(ethylene glycol)‐based doxorubicin‐loaded cores (BM‐PDs) can be used to target BMECs and cross the BBB. In vitro, the BM‐PDs effectively target BMECs and cross a BBB model. The BM‐PDs enter the BMECs via macropinocytosis, clathrin‐mediated endocytosis, caveolin‐mediated endocytosis, and membrane fusion, which result in excellent cellular uptake. The BM‐PDs also show excellent cellular uptake in brain tumor cells. In vivo, the BM‐PDs target BMECs, cross the BBB, accumulate in brain tumors, and efficiently kill tumor cells. Therefore, the proposed strategy has great therapeutic potential owing to its ability to cross the BBB to reach brain tumors. The blood‐brain barrier (BBB) is composed of tightly interconnected brain microvascular endothelial cells (BMECs), which hinder effective drug delivery to the glioblastoma (GBM). By coating with bEnd3‐line BMEC membrane, the DOX‐loaded BM‐PDs exhibit specific targeting properties toward BMECs and demonstrate efficient transcytosis across the BBB. These BM‐PDs display potent antitumor activity in an intracranial GBM model and this property is not restricted to certain GBM cell types.