David versus Goliath

Funding volumes provided by major Danish funding organizations in 2009. Values are presented both in U.S. dollars and Euros. LF, the Lundbeck Foundation. The Danish Council for Strategic Research (DCSR) had three programs in 2009, which related to health sciences or nano/biotechnology and are relevant for comparison: the programs for Health, Food and Welfare (HFW), for Individual, Disease and Society (IDS), and for Strategic Growth Technologies (SGT). Also displayed are the volumes of the Danish Council for Independent Research (DCIR), Natural Sciences (NS) and Medical Sciences (MS) as well as the total volume of funds distributed by the Danish Cancer Society (DCS).

Distribution of the three Nanomedicine Research Centers and associated Nanobiotechnology Centers throughout Denmark. Aarhus University hosts LUNA (the Lundbeck Foundation Nanomedicine Centre for Individualized Management of Tissue Damage and Regeneration) and the Interdisciplinary Nanoscience Center (iNANO), whereas the CBN (the Lundbeck Foundation Center for Biomembranes in Nanomedicine) and the NSC (Nano-Science Center) are located at the University of Copenhagen. NanoCAN (the Lundbeck Foundation Nanomedicine Research Center for Cancer Stem Cell Targeting Therapeutics), the NAC (Nucleic Acid Center), and MEMPHYS (Center for Biomembrane Physics) are at the University of Southern Denmark in Odense.

Concepts and strategies of the CBN. Biomembranes possess nanoscaled domains that differ in composition (1) and/or architecture (2), which modulates their functional properties. Via type VI secretion systems, bacteria secrete vesicles that contain quorum sensing factors and toxins for cell-cell communication within the species and for delivery of factors to host cells (3). The reciprocal processes of exocytosis and endocytosis via lipid vesicles take place during neurotransmitter-mediated communication between neurons, which employs exocytotic release from intracellular liposomal particles (4), inside-outside orientation (inverted). Lipid domain composition and architecture (1, 2) exert critical influences on these processes. The CBN will employ state-of-the-art tools to image and manipulate communication vesicles with nanoparticles (5), to create advanced nanobiosensors (6) and to utilize this knowledge for creating a new generation of drug delivery systems.

Research strategies in LUNA. The Center's research strategies comprise four major components. Nanoparticles and nanostructured surfaces modulating or mimicking pattern recognition processes are employed for cell-based therapies and three-dimensional scaffold-based tissue engineering. The approaches are supported by state-of-the-art bioimaging at the nanoscale and the development of nanodrug-delivery devices. Information gained from these efforts is funneled into drug design and validation, which finally uses animal models for proof of principle at the preclinical stage.

Schematic presentation of NanoCAN's research strategies. Core activities within the Center comprise the construction of cancer cells with cancer stem cell–specific molecular fingerprints, which consecutively are processed via high-throughput genome-wide siRNA screens and analyses via an advanced biochip format. In parallel, aptamers for targeting are generated and packaging of the nucleic acid–based drugs via self-assembly, liposomes, and solid nanospheres is tested. The optimal configurations are selected for integration of selected siRNA hits from high-throughput screening. The goal is to yield nanodrugs that would selectively kill cancer stem cells (red cells), thereby cutting off supply for the cancer cells (orange cells), leading to tumor eradication with only minimal adverse side effects on normal cells (blue cells) and normal adult stem cells (green cells).