Unit 3: Non-Liposomal Nanospheres

NanoCAN's UNIT 3 aims at developing and testing biocompatible and biodegradable non-liposomal nano delivery devices (NLNDD) for the delivery of nucleic acids, in particular siRNAs. The goal of the NLNDD is to (a) enhance the biostability of siRNA in vivo, (b) facilitate a selective uptake into cancer stem cells and (c) the release of bioactive siRNA into the cytosol of the target cells.

The siRNA will be condensed and encapsulated by biocompatible and biodegradable polymers forming nanospheres. The polymers will protect the siRNA from degradation by ribonucleases hereby enhancing their biostability. The surface of the nanospheres can be functionalized with targeting ligands, antibodies or aptamers that will facilitate a selective cellular uptake. The uptake mechanism will most likely be endocytosis, through which the NLNDDs are incorporated into endosomes. Thus the polymers of the delivery device have to be designed to allow for the siRNA to escape the endosomes, before the endosomes develop into lysosomes, where the siRNA will be degraded.

A spectrum of potential polymeric based carriers are scheduled and tested for easiness of production (at laboratory scale), size range and dispersity, as well as their ability to efficiently incorporate siRNAs (Fig. 1a). The devices are pushed through consecutive stages of evaluation, including siRNA delivery activity, basic cell toxicity, and coupling efficacy for targeting ligands (Fig. 1b). Delivery formats with targeting ligands are analyzed in "yes/no" cell lines, which are genetically engineered to either possess the respective receptor or to lack it. The most promising devices will be scheduled for in vivo testing in Unit 6.

 

unit3 fig1Aunit3 fig1B

Fig. 1. Experimental non-liposomal delivery devices. (a) Fluorescence readout obtained for the non-siRNA loaded particles (SCS) and the particles loaded with the fluorescently labeled siGLO siRNA. The increase of signal points to successful loading. (b) Fluorescence readout of the paricles before ("Particles") and after coupling of a fluorescently labeled aptamer to the particle surface. The increased signal points to successful coupling.

 

sdulogo

Search

 
 
 
 

Joomla Templates by Joomla51.com