Autor: |
Kretzmann JA; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia., Evans CW; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia., Feng L; ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Wollongong, NSW 2522, Australia., Lawler NB; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia., Norret M; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia., Higgins MJ; ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Wollongong, NSW 2522, Australia., Iyer KS; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. |
Abstrakt: |
Successful intracellular delivery of therapeutics requires interactions at several liquid-solid interfaces, including cell surface, endosomal membranes, and-depending on the therapeutic-the nuclear membrane. Understanding the dynamics of polymer kinetics at the liquid-solid interface is fundamental for the design of polymers for such biomedical delivery applications. However, the effect of polymer architecture and charge density on polymer kinetics is not readily investigated using routine techniques, and the role of such parameters in the context of gene delivery remains unknown. We adopted a synthetic strategy which enabled the systematic manipulation of charge density, flexibility, and molecular weight using a dendronized linear polymeric architecture. High-speed atomic force microscopy (HS-AFM) was used as a label-free method to directly observe the polymers' dynamic properties, such as velocity, displacement, and diffusion, in physiologically relevant conditions. Importantly, we found that the physical parameters measured by HS-AFM relate to the transfection potential of the individual polymers and may be a valuable tool in screening structural polymer variants. |