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Development of advanced fluorescence microscopy methods for studying the structure, transport and stability of nanomedicines for gene therapy of the retinal pigment epithelium (R-2835)

The Retinal Pigment Epithelium (RPE) is the outer blood-retinal barrier in the eye beneath the neural retina. As the RPE cells are related to a number of genetic ocular diseases, they are interesting candidates for nucleic acid treatment. Several types of nanomedicines are being evaluated for delivering nucleic acids to the RPE cells. Despite their huge potential, progress in nanomedicine development is slow due to a limited knowledge of their structure, transport and stability during the various phases of the delivery process. To address this issue we propose to develop several advanced fluorescence microscopy methods. We will develop novel methods based on dual-color Single Particle Tracking (SPT) microscopy for evaluating the efficiency with which nucleic acids can be incorporated into nanomedicines. The nanomedicine internal structure will be studied by the newest super-resolution microscopy techniques such as STORM and STED. The transport and stability of nanomedicines in vitreous gel, neural retina and inside living RPE cells will be studied by a newly developed fluorescence lifetime raster image correlation spectroscopy (FL- RICS) method and dual color 3-D SPT. The knowledge gained in this project from the new microscopy methods will enable a rational and efficient development of nanomedicines for nucleic acid therapy.
Date:1 Jan 2011 →  31 Dec 2014
Keywords:fluorescence lifetime imaging microscopy (FLIM)
Disciplines:Electrical and electronic engineering, (Bio)medical engineering, Computer engineering, information technology and mathematical engineering, Basic sciences, Clinical sciences, Pharmaceutical sciences, Translational sciences