Gene therapy shows much promise in treating many inheritable and acquired diseases, but challenges remain in the design of gene vectors with low cytotoxicity and high transfection efficiency. Elucidating the structure-function relationship of non-viral polymer-based gene carriers is crucial for improving the design and performance of safe and effective gene therapy approaches. The cationic poly(2-aminoethyl methacrylate) (PAEM) containing primary amino side groups is an attractive carrier for gene delivery. This study focuses on four PAEM-based polycations with well-defined molecular weight and chain architecture. The polymers include three cyclodextrin (CD)-cored star-shaped PAEM polycations (s-PAEM), synthesized by atom transfer radical polymerization (ATRP), and a linear PAEM polycation (l-PAEM), synthesized via activators regenerated by electron transfer (ARGET) ATRP. All four polycations could condense plasmid DNA (pDNA) into spherical polyplexes with small sizes (<200 nm). The polyplexes showed excellent stability during storage and were able to resist electrostatic destabilization. The cytotoxicity of these polycations was depended on dose and target cell type and was influenced by molecular weight and chain architecture, yet the polyplexes showed little cytotoxicity regardless of the type of polymer used. The transfection efficiency of PAEM polycations was highly dependent upon molecular weight, molecular architecture (star versus linear) and target cell type. In most cases, polyplexes formed by high-molecular-weight s-PAEM performed the best. Moreover, at a specific N/P ratio, the transfection efficiency mediated by s-PAEM was higher in MCF-7 breast cancer cells than in COS-7 fibroblast-like cells, but such cell-type dependence was not obvious for l-PAEM. These findings indicate that the star-shaped PAEM polycations could be promising gene carriers for gene therapy applications.
Bibliographical noteFunding Information:
This work was supported by the Special Program for High-Tech Leader & Team of the City of Tianjin , the Key Innovation Team Project on Immunoreactive Biomaterials as part of the Tianjin Innovation Promotion Plan, the Natural Science Foundation of Tianjin ( 17JCYBJC29100 and 17JCZDJC37400 ), and the Innovation Fund for Medical Sciences ( 2017-I2M-1-016 ) from the Chinese Academy of Medical Sciences (CAMS) .
© 2019 Elsevier B.V.
- Gene transfection
- Poly(2-aminoethyl methacrylate) (PAEM)
- Star-shaped polycation
- Structure-function relationship