Bioengineered Neutrophils for Smart Response in Brain Infection Management.

Autor: Zhou A; National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, School of Physics, Nanjing University, Nanjing, 210093, China., Kong D; Department of Neurology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, 211000, China., Zhou X; National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Chemistry and Biomedicine Innovation Center, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210093, China., Liu Y; Department of Neurology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, 211000, China., Zhang Y; National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Chemistry and Biomedicine Innovation Center, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210093, China., Li J; Department of Neurology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, 211000, China., Xu Y; National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Chemistry and Biomedicine Innovation Center, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210093, China., Ning X; National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Chemistry and Biomedicine Innovation Center, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210093, China.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2024 May; Vol. 36 (18), pp. e2311661. Date of Electronic Publication: 2024 Jan 28.
DOI: 10.1002/adma.202311661
Abstrakt: Brain infections, frequently accompanied by significant inflammation, necessitate comprehensive therapeutic approaches targeting both infections and associated inflammation. A major impediment to such combined treatment is the blood-brain barrier (BBB), which significantly restricts therapeutic agents from achieving effective concentrations within the central nervous system. Here, a neutrophil-centric dual-responsive delivery system, coined "CellUs," is pioneered. This system is characterized by live neutrophils enveloping liposomes of dexamethasone, ceftriaxone, and oxygen-saturated perfluorocarbon (Lipo@D/C/P). CellUs is meticulously engineered to co-deliver antibiotics, anti-inflammatory agents, and oxygen, embodying a comprehensive strategy against brain infections. CellUs leverages the intrinsic abilities of neutrophils to navigate through BBB, accurately target infection sites, and synchronize the release of Lipo@D/C/P with local inflammatory signals. Notably, the incorporation of ultrasound-responsive perfluorocarbon within Lipo@D/C/P ensures the on-demand release of therapeutic agents at the afflicted regions. CellUs shows considerable promise in treating Staphylococcus aureus infections in mice with meningitis, particularly when combined with ultrasound treatments. It effectively penetrates BBB, significantly eliminates bacteria, reduces inflammation, and delivers oxygen to the affected brain tissue, resulting in a substantial improvement in survival rates. Consequently, CellUs harnesses the natural chemotactic properties of neutrophils and offers an innovative pathway to improve treatment effectiveness while minimizing adverse effects.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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