Inactive Trojan Bacteria as Safe Drug Delivery Vehicles Crossing the Blood–Brain Barrier

• DOI: 10.1021/acs.nanolett.3c00563
• Publication Date: 2023-05-02T17:19:17Z
• Authors: Jianping Lu; Jiali Ding; Binbin Chu; Chen Ji; Qian Zhang; Yanan Xu; Bin Song; Houyu Wang; Yao He
• Keywords: Brain dead; Efflux

Escherichia coli K1 (EC-K1) can bypass the blood–brain barrier (BBB) and cause meningitis. Excitingly, we find "dead EC-K1" safely penetrate BBB because they retain intact structure chemotaxis of live EC-K1, while losing their pathogenicity. Based on this, develop a safe EC-K1"-based drug delivery system, in which EC-K1 engulf maltodextrin (MD)-modified therapeutics through bacteria-specific MD transporter pathway, followed by inactivation via UV irradiation. We demonstrate that dead bacteria could carry (e.g., indocyanine green (ICG)) together after intravenous injection into mice, delivering ∼3.0-fold higher doses brain than free ICG under same conditions. What is more, all mice remain healthy even 14 days ∼109 CFU inactive bacteria. As proof concept, developed strategy enables therapy bacterial meningitis glioblastoma mice.