Lipoplexes to Deliver Oligonucleotides in Gram-Positive and Gram-Negative Bacteria: Towards Treatment of Blood Infections

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Pereira, S (Author) Other; Santos, RS (Author) Other; Moreira, L (Author) Other; Guimaraes, N (Author) FEUP; Gomes, M (Author) Other; Zhang, HY (Author) Other; Remaut, K (Author) Other; Braeckmans, K (Author) Other; De Smedt, S (Author) Other; Azevedo, NF (Author) FEUP

Journal

Title: Pharmaceutics

Vol. 24

Final page: 989

ISSN: 1999-4923

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 5 Citations

Other information

Authenticus ID: P-00V-7MP

DOI: 10.3390/pharmaceutics13070989

Abstract (EN): Bacterial resistance to antibiotics threatens the ability to treat life-threatening bloodstream infections. Oligonucleotides (ONs) composed of nucleic acid mimics (NAMs) able to inhibit essential genes can become an alternative to traditional antibiotics, as long as they are safely transported in human serum upon intravenous administration and they are carried across the multilayered bacterial envelopes, impermeable to ONs. In this study, fusogenic liposomes were considered to transport the ONs and promote their internalization in clinically relevant bacteria. Locked nucleic acids and 2 '-OMethyl RNA were evaluated as model NAMs and formulated into DOTAP-DOPE liposomes followed by post-PEGylation. Our data showed a complexation stability between the post-PEGylated liposomes and the ONs of over 82%, during 24 h in native human serum, as determined by fluorescence correlation spectroscopy. Quantification by a lipid-mixing assay showed that liposomes, with and without post-PEGylation, fused with all bacteria tested. Such fusion promoted the delivery of a fraction of the ONs into the bacterial cytosol, as observed by fluorescence in situ hybridization and bacterial fractionation. In short, we demonstrated for the first time that liposomes can safely transport ONs in human serum and intracellularly deliver them in both Gram-negative and -positive bacteria, which holds promise towards the treatment of bloodstream infections.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14