Engineered liposomes to deliver nucleic acid mimics in Escherichia coli

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Luís Moreira (Author) Other; Nuno Guimarães (Author) FEUP; Sara Pereira (Author) Other; Rita S. Santos (Author) Other; Joana A. Loureiro (Author) FEUP; Rui M. Ferreira (Author) Other; Maria do Céu Figueiredo (Author) FMUP; Maria do Carmo Pereira (Author) Other; Nuno F. Azevedo (Author) FEUP

Journal

Title: Journal of Controlled Release

Vol. 355

Pages: 489-500

ISSN: 0168-3659

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus

Other information

Authenticus ID: P-00X-YEX

DOI: 10.1016/j.jconrel.2023.02.012

Abstract (EN): Antisense oligonucleotides (ASOs) composed of nucleic acid mimics (NAMs) monomers are considered as po-tential novel therapeutic drugs against bacterial infections. However, bacterial envelopes are generally imper-meable to naked oligonucleotides. Herein, liposomes loaded with NAMs-modified oligonucleotides (LipoNAMs) were evaluated to deliver ASOs in Escherichia coli. Specifically, we tested several surface modifications that included methoxyPEG conjugated to different lipid anchors or modification of the PEG distal ends with mal-eimide groups and antibodies. MethoxyPEG coated LipoNAMs showed low delivery efficiency for most bacteria, but maleimide-functionalized PEG LipoNAMs were able to deliver ASOs to nearly half of the bacterial population. Conjugation of antibodies to maleimide-functionalized PEG LipoNAMs increased 1.3-fold the delivery efficiency, enhancing the selectivity towards E. coli and biocompatibility. This work demonstrated for the first time that the coupling of antibodies to PEGylated liposomes can significantly improve the delivery of ASOs in E. coli, which might bring alternative routes for the treatment of bacterial infections in the future.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12