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By linking a drug to a special transport medium, it is possible to target that drug precisely where it is needed: a diseased organ or tumour, for example. But the transport medium must meet certain strict conditions. Producing such complex molecules for use in chemotherapy is the specialist field of the Biomedical Chemistry department.

Paracetamol and aspirin work quickly and are often very effective. However, they are anything but 'targeted'. If you take a pill for your headache, you might also lose some feeling in your little toe. In the case of relatively harmless painkillers, this is not such a great problem. The side effects of chemotherapy are far more irksome. While the drugs ensure that cancer cells do not have a chance to multiply, they can also result in hair loss, extreme nausea and immune deficiency. This is because chemotherapy drugs, like aspirin, are 'systemic': they enter the patient's bloodstream and are carried to every part of the body.

If an anti-cancer drug can be released only in the immediate proximity of the tumour it is intended to fight, side effects can be vastly reduced. It will be possible to do just this using special transport molecules which act as a 'postal service', packaging the aggressive yet fragile drugs and delivering them to precisely the right address: the tumour.

However, there are a number of requirements. The transport molecules must also circulate in the blood before reaching their final destination, and must not be intercepted by, say, the liver. They must arrive precisely where they are needed and must then be able to 'recognize' a sick cell, perhaps on the basis of temperature or acidity. They must then be able to penetrate that cell. Once inside, the pharmaceutical 'parcel' must be automatically unwrapped as the transport molecule responds to the specific conditions within the damaged cell. Having completed its delivery, the transport molecule must be broken down and eliminated from the body so that it causes no ill effects.

To find a transport molecule which meets so many different requirements is an enormous scientific challenge. Nevertheless, it is one to which the University of Twente has successfully risen. Researchers from the Biomedical Chemistry department discovered the potential of polyamidoamines as transport molecules in chemotherapy. Polyamidoamines appear to be able to transport DNA and siRNA, forms of genetic material which offer the promise of new forms of chemotherapy. However, like other anti-cancer drugs, they are harmful to healthy cells. If 'packaged' within polyamidoamines, they can be targeted at cancerous tissue and released only where they are needed.

The researchers are now working to refine their polyamidoamines. The requirements sometimes appear to conflict. For example, increasing the positive electrical charge of the polyamidoamines increases their 'packaging' potential but also makes them more toxic. It will be worthwhile to continue seeking solutions to this problem. However, it will be some time before the transport molecules are actually in clinical use. In the world of pharmaceutical development, it can take ten years or more before a new medicine is produced on any large scale.

siRNA in chemotherapy
Our DNA determines our genetic, or hereditary, characteristics. It is part of the nucleus of every cell in our bodies. DNA contains a 'code' for the proteins which make up the remainder of the cell. Because DNA cannot leave the cell nucleus, the code for each protein is copied onto a messenger molecule - mRNA - which can. The mRNA is a long molecule rather like a string of beads. Imagine there are four colours of bead, which can be arranged to represent the code contained in the DNA. The mRNA then combines with other substances to create the specific protein for which it is coded. Amino acids, the basic building blocks of protein, are linked together one by one according to the code.

The process of building the protein can be disrupted by 'short interference RNA', or siRNA. This is a short section of RNA which can readily attach itself to part of the code. The protein cannot then take its intended form. This property of siRNA is what makes it so suitable for use in chemotherapy. It could, for example, be used to stop the creation of the proteins which make up the blood vessels which a tumour needs to grow. No protein, no blood vessels, no tumour!