Third party funded individual grant
Start date : 01.01.2018
End date : 31.12.2019
Advances in nanotechnology and biotechnology have seen incredible developments in nano-shell technologies, e.g. PLA, PEG-coated and functionalized micro- and nanoparticles (synthetic polymers) for sustained drug delivery. One still unresolved problem lies within the target specificity of such drug delivery vehicles. For instance, spray-coated polymer-shells will passively diffuse throughout the systemic circulation and dissolve their active compound in an unspecific manner. Apart from polymers, synthetically derived lipid vesicles have the advantage of an amphiphilic character which attracts them to lipophilic phases, e.g. cell membranes. Such vesicles could be designed to encapsulate active drug compounds, but in addition, the lipid layer could be used to transport ion channel and membrane transporters to target cells. To direct the vehicles to target cells in a specific manner, additionally anchored surface-targeted antibodies will be employed. We propose a highly innovative approach in synthetic biotechnology to address the following goals:
1) To chemically synthesize lipid vesicles containing cytotoxic drugs (e.g. methotrexate) and to compare their drug-release profile in vitro in comparison to micro-patterned polymer-vesicles
2) To functionalize lipid vesicles with surface-active amphiphilic phases and glycocalyx in order to incorporate ion channel proteins into their membrane (e.g. bacterial mechano-sensitive ion channels, MscL from E. coli); to counter-validate this approach also in micro-patterned polymer vesicles
3) To additionally provide a stable protein-S coating to increase binding of Fc-component antibodies to the lipid vesicles and micro-patterned polymer vesicles
4) To incorporate either vesicle lineage as a hetero-disperse phase into mammalian cells with a specificity determined by the respective tissue surface antigen-antibody coated onto the vesicle carrier
5) To assess ion channel activation of the incorporated vesicle membrane by appropriate stimuli in vitro and determine intracellular release of the inner drug layers
Through the combined expertise of synthetic chemistry with nano-biotechnology, our new collaborative initiative provides a new, highly innovative research venue for developing a novel type of biotech-drug applicability with high tissue specificity that may be further translated into cancer treatment.