Bioreducible-Cationic Poly(amido amine)s for Enhanced Gene Delivery and Osteogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells.
The development of efficient and safe gene delivery carriers has been a major challenge in the clinical application of non-viral gene therapy. Herein, we report novel bioreducible poly(amido amine)s for the efficient delivery of genetic material such as plasmid DNA. A library of 34 different bioreducible polymer compounds was synthesized and screened to find lead materials for in vitro gene transfection. Our lead material (CBA-106) allows effortless polyplex formation with genetic materials by electrostatic interactions at the weight ratio of 1:5 (DNA/polymer). Polyplexes were further characterized by DLS and AFM analysis. Enhanced serum stability and bioreducibility under physiological conditions were confirmed, in addition to low cellular cytotoxicity. When compared with a commercially available gene delivery carrier (Lipofectamine 2000), CBA-1 06 shows comparable or even surpassing gene transfection efficiency. Furthermore, BMP-2 plasmids were efficiently delivered to tonsil-derived mesenchymal stem cells (TMSCs) for osteogenic commitment in vitro and in vivo. Taken together, our results clearly demonstrate the potential of novel bioreducible polymeric systems for gene delivery applications. We suggest that our system can provide a valuable platform for the broad application of gene regulation in cell therapy and regenerative medicine.
Hansaem
H
Jeong
Eun-Seo
ES
Lee
Giyoung
G
Jung
Jungha
J
Park
Byeongmoon
B
Jeong
Kyung Ha
KH
Ryu
Nathaniel S
NS
Hwang
Hyukjin
H
Lee
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002412:Cations; D002454:Cell Differentiation; D004247:DNA / Q000378:metabolism; D000067493:Dynamic Light Scattering; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018625:Microscopy, Atomic Force; D010012:Osteogenesis; D014066:Palatine Tonsil / Q000166:cytology*; D010957:Plasmids / Q000378:metabolism; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection
D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D002412:Cations; C531249:Poly(amidoamine); D011073:Polyamines; D049452:Green Fluorescent Proteins; D004247:DNA