DNA Polyplexes of a Phosphorylcholine-Based Zwitterionic Polymer for Gene Delivery

• Published in: Pharmaceutical research 2020-09, Vol.37 (9), p.176-176, Article 176
• Main Authors: Dave, Kandarp M., Han, Linjiang, Jackson, Meredith A., Kadlecik, Lindsay, Duvall, Craig L., S Manickam, Devika
• Format: Article
• Language: English
• Subjects: Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cell adhesion & migration; Cell Line; Cell lines; Cell migration; Cell Proliferation; Deoxyribonucleic acid; DNA; DNA - metabolism; Flow cytometry; Gene transfer; Gene Transfer Techniques; Genetic research; Glioblastoma; Glioblastoma cells; Glioma cells; Gliomas; Humans; Infection; Interferon-beta - metabolism; International economic relations; Luciferase; Medical Law; Pharmacology/Toxicology; Pharmacy; Phosphorylcholine; Plasmids; Polymer industry; Polymers; Polymers - chemistry; Research Paper; Surface active agents; Transfection; Transfection - methods; Zeta potential; β-Interferon
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-020-02899-5

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-β1) 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-β1 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.