Inactive Trojan Bacteria as Safe Drug Delivery Vehicles Crossing the Blood-Brain Barrier.
Nano Lett
; 23(10): 4326-4333, 2023 05 24.
Article
em En
| MEDLINE
| ID: mdl-37130058
ABSTRACT
Escherichia coli K1 (EC-K1) can bypass the blood-brain barrier (BBB) and cause meningitis. Excitingly, we find the "dead EC-K1" can safely penetrate the BBB because they retain the intact structure and chemotaxis of the live EC-K1, while losing their pathogenicity. Based on this, we develop a safe "dead EC-K1"-based drug delivery system, in which EC-K1 engulf the maltodextrin (MD)-modified therapeutics through the bacteria-specific MD transporter pathway, followed by the inactivation via UV irradiation. We demonstrate that the dead bacteria could carry therapeutics (e.g., indocyanine green (ICG)) and together bypass the BBB after intravenous injection into the mice, delivering â¼3.0-fold higher doses into the brain than free ICG under the same conditions. What is more, all mice remain healthy even after 14 days of intravenous injection of â¼109 CFU of inactive bacteria. As a proof of concept, we demonstrate the developed strategy enables the therapy of bacterial meningitis and glioblastoma in mice.
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Base de dados:
MEDLINE
Assunto principal:
Barreira Hematoencefálica
/
Meningites Bacterianas
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article