DNA Polyplexes of a Phosphorylcholine-Based Zwitterionic Polymer for Gene Delivery
DNA polyplexes, glioblastoma, interferon-beta1, transfection, zwitterionic phosphorylcholine polymer
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.
Dave, K., Han, L., Jackson, M., Kadlecik, L., Duvall, C., & S Manickam, D. (2020). DNA Polyplexes of a Phosphorylcholine-Based Zwitterionic Polymer for Gene Delivery. Pharmaceutical Research, 37 (9). https://doi.org/10.1007/s11095-020-02899-5