| Autor: |
Franck CO; BioNano Engineering Lab, Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, UK. lf389@cam.ac.uk., Bistrovic Popov A; BioNano Engineering Lab, Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, UK. lf389@cam.ac.uk., Ahmed I; BioNano Engineering Lab, Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, UK. lf389@cam.ac.uk., Hewitt RE; Department of Veterinary Medicine, University of Cambridge, Madingley Rd, Cambridge CB3 0ES, UK., Franslau L; Institut für Physikalische Chemie, Georg-August-Universität Göttingen, Tammanstraße 6, Göttingen 37077, Germany., Tyagi P; AstraZeneca, One MedImmune Way, Gaithersburg, MD 20878, USA., Fruk L; BioNano Engineering Lab, Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, UK. lf389@cam.ac.uk. |
| Abstrakt: |
The design of nanomaterial-based nucleic acid formulations is one of the biggest endeavours in the search for clinically applicable gene delivery systems. Biopolymers represent a promising subclass of gene carriers due to their physicochemical properties, biodegradability and biocompatibility. By modifying melanin-like polydopamine nanoparticles with poly-L-arginine and poly-L-histidine blends, we obtained a novel catch-and-release gene delivery system for efficient trafficking of pDNA to human cells. A synergistic interplay of nanoparticle-bound poly-L-arginine and poly-L-histidine was observed and evaluated for pDNA binding affinity, cell viability, gene release and transfection. Although the functionalisation with poly-L-arginine was crucial for pDNA binding, the resulting nanocarriers failed to release pDNA intracellularly, resulting in limited protein expression. However, optimal pDNA release was achieved through the co-formulation with poly-L-histidine, essential for pDNA release. This effect enabled the design of gene delivery systems, which were comparable to Lipofectamine in terms of transfection efficacy and the catch-and-release surface modification strategy can be translated to other nanocarriers and surfaces. |
