4Dimensions Atomic Force Microscopy Investigation of the Packing and
Un-packing of Dendritic-DNA Nanoplexes
Hosam G Abdelhady
Assistant Professor-Faculty of Pharmacy-Taibah University-300001-Al Mdinah Almunawarrah-SA
Visiting Professor- Cellular Engineering & Nano-Therapeutics Laboratory- University of Michigan-MI 48109-USA
Abstract:
The need to protect DNA from enzymatic digestion is one of the basic targets of therapeutic DNA delivery and a standard test for any proposed delivery vector. The currently applied in vitro methods, however, provide no direct link between the molecular morphology/behavior of the polyplexes and their success in protecting the DNA from the enzymes. Thus, hindering the rational design of successful gene delivery nano-devices. Here we apply 4 dimensions atomic force microscopy in liquid to visualize at the molecular scale and in real time, the effect of DNase I enzyme on generation 4 polyamidoamine dendrimers (G4) complexed with DNA. These complexes are revealed to be dynamic in nature showing a degree of mobility, in some cases revealing the addition and loss of dendrimers to individual complexes. The formation of the G4-DNA nanoplexes is observed to provide a degree of protection to the DNA. This protection is related to the structural morphology of the formed complex, which in itself shown to be dependent on the dendrimer loading and the time allowed for complex formation.
Acknowledgments:
We thank the Egyptian Government, NODCAR, and The University of Nottingham for funding.
keywards: Atomic force microscopy, Dendrimers, Gene therapy, Nanoplexes
