DNA Polyplexes of a Phosphorylcholine-Based Zwitterionic Polymer for Gene Delivery.
Pharm Res
; 37(9): 176, 2020 Aug 28.
Article
em En
| MEDLINE
| ID: mdl-32860072
ABSTRACT
PURPOSE:
We tested polyplexes of a diblock polymer containing a pH-responsive, endosomolytic core (dimethylaminoethyl methacrylate and butyl methacrylate; DB) and a zwitterionic Poly (methacryloyloxyethyl phosphorylcholine) (PMPC) corona for the delivery of plasmid DNA (pDNA) to glioblastoma cells.METHODS:
We studied the physicochemical characteristics of the DNA polyplexes such as particle hydrodynamic diameter and surface potential. Cytocompatibility of free PMPC-DB polymer and pDNA polyplexes with U-87MG and U-138MG glioma cell lines were evaluated using the ATP assay. The transfection activity of luciferase pDNA polyplexes was measured using a standard luciferase assay. Anti-proliferative, apoptotic, and cell migration inhibitory activities of PMPC-DB/Interferon-beta (IFN-ß1) pDNA polyplexes were examined using ATP assay, flow cytometry, and wound closure assay, respectively.RESULTS:
PMPC-DB copolymer condensed pDNA into nanosized polyplexes. DNA polyplexes showed particle diameters ranging from ca. 100-150 nm with narrow polydispersity indices and near electroneutral zeta potential values. PMPC-DB/Luciferase pDNA polyplexes were safe and showed an 18-fold increase in luciferase expression compared to the gold standard PEI polyplexes in U-87MG cells. PMPC-DB/IFN-ß1 polyplexes induced apoptosis, demonstrated anti-proliferative effects, and retarded cell migration in glioblastoma cells.CONCLUSION:
The results described herein should guide the future optimization of PMPC-DB/DNA delivery systems for in vivo studies.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
DNA
/
Transfecção
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article