Drug Targeting

The research objectives of the Drug Targeting group within the Department of Nanomedicine & Drug Targeting focus on the design and testing of novel strategies for cell-specific delivery of therapeutic compounds. In general, drugs are taken up by many cell types throughout the body which often leads to side effects and to a reduced effectivity of the compound. For some diseases and some drugs, cell–specific delivery of drugs is crucial to achieve a therapeutic effect.

Some diseases that greatly benefit from a targeted approach are chronic inflammatory and sclerotic processs and cancers. The diseases of interest within the group are therefore liver fibrosis, neoplastic processes in particular those characterized by the formation of stromal tissue and several chronic inflammatory reactions in other organs (e.g. Colitis Ulcerosa, glomerulosclerosis).

The research group designs and evaluates unique nanocarriers that consist of a therapeutic entity coupled to a homing device. The homing device provides the cell specificity to the drug or therapeutic entity and is designed by the group. In general, our carriers are proteins that are equiped with receptor recognizing peptides or special sugar moieties. The peptides or sugar moieties bind to particular receptors that are abundantly expressed on target cells within the diseased tissue. After binding of the nanocarrier to the target cell, the therapeutic entity is taken up and, if properly designed, released in its active form within this cell.

Obviously it is essential to identify the target cell or key pathological process within diseased tissue solid expertise on Pathology and Immunology is essential. The research within our group is on the cutting edge of the Pharmaceutical Sciences and the Medical Biology. In our group we have focussed on growth factor receptors such as the Platelet Derived Growth Factor Receptor, the Insulin-Like Growth Factor II Receptor and the Collagen type IV receptor.These receptors are abundantly expressed on fibroblast-like cells. These particular cells play a key role during fibrotic and sclerotic diseases like liver cirrrhosis, atherosclerosis, renal fibrosis, lung fibrosis and certain types of cancer.

The Drug targeting team has developed the first cell-selective drug carriers to myofibroblast-like cells. New nanocarriers were patented which appeared to be applicable for the selective delivery of therapeutic and diagnostic compounds to this important cell–type during liver fibrosis and several types of cancer. We tested these compound in vitro and in animal models of disease. Clinical trials with some of our key compounds are now in preparation.

We also discovered the endotoxin-detoxifying properties of the enzyme alkaline phosphatase. This enzyme is present is all tissues of the body but its function has been completely obscure. This discovery formed the basis for new drugs against sepsis and inflammatory bowel diseases which are now tested in clinical trials (phase II) in several European countries.

The Drug Targeting team produced several patents which are now being used by several pharmaceutical companies. In fact, two patents directly led to the foundation of spin-off companies (in 2001 and 2003) which were both listed in the top 25 of most innovative biotech companies in The Netherlands in 2007 (FEM-Magazine, June 2007).

Our research group received many European grants from the Marie Curie program as well as prestigious grants via the Innovative Incentive Scheme of the Dutch scientific organisations STW and NWO (Vidi and Vici grants). Next to the funding of research activities by pharmaceutical companies and other competitive programs these grants form the basis for our innovative research programs on new cell-selective drugs.