Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells.

PPRH apoptosis cancer cell viability delivery hairpin mammalian cell stable transfection therapeutic oligonucleotide transfection agent

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
27 Jan 2023
Historique:
received: 02 01 2023
revised: 18 01 2023
accepted: 20 01 2023
entrez: 25 2 2023
pubmed: 26 2 2023
medline: 26 2 2023
Statut: epublish

Résumé

One of the most significant limitations that therapeutic oligonucleotides present is the development of specific and efficient delivery vectors for the internalization of nucleic acids into cells. Therefore, there is a need for the development of new transfection agents that ensure a proper and efficient delivery into mammalian cells. We describe the synthesis of 1,3,5-tris[(4-oelyl-1-pyridinio)methyl]benzene tribromide (TROPY) and proceeded to the validation of its binding capacity toward oligonucleotides, the internalization of DNA into the cells, the effect on cell viability, apoptosis, and its capability to transfect plasmid DNA. The synthesis and chemical characterization of TROPY, which can bind DNA and transfect oligonucleotides into mammalian cells through clathrin and caveolin-mediated endocytosis, are described. Using a PPRH against the antiapoptotic TROPY is an efficient transfecting agent that allows the delivery of therapeutic oligonucleotides, such as PPRHs and plasmid DNA, inside mammalian cells.

Sections du résumé

BACKGROUND BACKGROUND
One of the most significant limitations that therapeutic oligonucleotides present is the development of specific and efficient delivery vectors for the internalization of nucleic acids into cells. Therefore, there is a need for the development of new transfection agents that ensure a proper and efficient delivery into mammalian cells.
METHODS METHODS
We describe the synthesis of 1,3,5-tris[(4-oelyl-1-pyridinio)methyl]benzene tribromide (TROPY) and proceeded to the validation of its binding capacity toward oligonucleotides, the internalization of DNA into the cells, the effect on cell viability, apoptosis, and its capability to transfect plasmid DNA.
RESULTS RESULTS
The synthesis and chemical characterization of TROPY, which can bind DNA and transfect oligonucleotides into mammalian cells through clathrin and caveolin-mediated endocytosis, are described. Using a PPRH against the antiapoptotic
CONCLUSIONS CONCLUSIONS
TROPY is an efficient transfecting agent that allows the delivery of therapeutic oligonucleotides, such as PPRHs and plasmid DNA, inside mammalian cells.

Identifiants

pubmed: 36839742
pii: pharmaceutics15020420
doi: 10.3390/pharmaceutics15020420
pmc: PMC9960667
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Ministerio de Ciencia e Innovacion
ID : PID2021-122271OB-I00

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Auteurs

Ana Delgado (A)

Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.

Rosa Griera (R)

Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.

Núria Llor (N)

Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.

Ester López-Aguilar (E)

Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.

Maria Antònia Busquets (MA)

Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
Nanoscience and Nanotechnology Institute, IN2UB, University of Barcelona, 08028 Barcelona, Spain.

Véronique Noé (V)

Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
Nanoscience and Nanotechnology Institute, IN2UB, University of Barcelona, 08028 Barcelona, Spain.

Carlos J Ciudad (CJ)

Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
Nanoscience and Nanotechnology Institute, IN2UB, University of Barcelona, 08028 Barcelona, Spain.

Classifications MeSH