The main goal of UNIT 1 is to develop a liposome-based platform for active and selective delivery of condensed siRNA particles to cancer stem cells in vivo. This platform should further be capable of (1) efficient encapsulation and triggered release of bioactive siRNA complexes, and (2) enhanced biostability in vivo.
Division 2: Nanoparticles
So-called siRNAs are the preferred active component of the nano-drugs created and explored within NanoCAN. These small nucleic acid molecules can potently inhibit every gene or functional RNA of choice within a cell. A yet unsolved problem is the delivery of siRNAs, however. Major problems include the instability, unfavorable pharmacological properties, and the targeted delivery to a tissue or cell of choice.
DIVISION 2 pursues three basic strategies to improve the situation:
- Unit 1 deals with liposomal delivery formats, building up on basic research performed in the Center of Excellence MEMPHYS
- Unit 2 employs cutting-edge nucleic acid chemistry and devices, grasping back to basic research performed in the Center of Excellence NAC
- Unit 3 explores alternative delivery formats, which are of synthetic or natural origin
The main goal of NanoCAN's UNIT 2 is to develop LNA-containing aptamers with the ability to bind cancer stem cells with high affinity and specificity. Once developed, aptamers will be attached to the outside of the liposomal devices (Unit 1) or the non-liposomal nanospheres (Unit 3) where they will act as targeting devices for the particles. A third strategy includes the construction of aptamer-siRNA chimeras, i.e. of nucleic acid molecules, in which the siRNA is directly coupled to the aptamer via a linker region.
NanoCAN's UNIT 3 aims at developing and testing biocompatible and biodegradable non-liposomal nano delivery devices for the delivery of nucleic acids, in particular siRNAs. A spectrum of potential carriers is scheduled and tested for easiness of production (at laboratory scale), size range and dispersity, as well as their ability to efficiently incorporate siRNAs