Targeted cancer drugs can distinguish between healthy and diseased cells

Image credit: Gundula Vogel, Pixabay

Drug treatment for many diseases often balances the need for high enough drug levels to give a therapeutic benefit against the concurrent increase in the risk of side effects. For example, toxic therapies such as chemotherapy drugs need to be administered at high doses to target and destroy highly replicating cells. However, this results in many of the undesirable side effects of chemotherapy as highly replicating cells include not just cancer cells, but also hair follicle and intestinal cells, resulting in hair loss and nausea.

This inability of drugs to discriminate between health and unhealthy cells is a common problem for standard drug administration, and so scientists have been searching for a method to develop targeted medications that can make this distinction, thereby only delivering the drug dose to diseased cells. This will potentially allow for more effective drug treatment regimes as higher doses could be delivered without triggering toxic side effects.

One method to create targeted drug treatments is to incorporate active drug molecules into nanoparticles (engineered particles between 1 and 100 nanometres in diameter) that contain a trigger so that the drug molecules are only released in specific circumstances. The nanoparticles themselves must be non-toxic, not induce an immune reaction, naturally break down or be excreted from the body, have a long circulation time in the body, and be cost effective.

A study of the application of nanoparticles for targeted drug therapies was published in August by researchers as the Technical University of Munich and the KTH Royal Institute of Technology in Stockholm. This paper reports a novel method of targeted drug delivery by packaging the drug molecules into nanoparticles containing synthetic DNA and mucins, which release active drug particles into cancerous, but not healthy, cells.

MicroRNAs found at very high levels in cancer cells can trigger the release of active drug molecules into these cells, but not in healthy cells that do not contain the microRNAs.

Mucins are proteins that form the main component of the mucus found in normal mucus membranes of the gastrointestinal tract. Therefore, because they are naturally occurring in mammals, they do not elicit an immune reaction and they can be broken down by the cell. When mixed with drug molecules and glycerol, the mucins fold up and enclose the drug in a reversible manner.

Synthetic DNA molecules were then added to the mucins to stabilise the nanoparticle and to give it specificity for a particular type of diseased cell. This synthetic DNA is chemically engineered in the laboratory and does not encode any genes, unlike naturally occurring DNA. Instead, these strands bind to both the mucin particle and to each other. This stabilises the folded mucin particle until it encounters the correct “key”, triggering mucin unfolding and drug release into diseased cells.

In this study, the “key” was engineered to be specific types of microRNAs. These are found in all cells, where they have roles in the regulation of gene expression. There are many different types of microRNAs found in a range of environments, including different cell types and a range of diseases. The researchers in this study used microRNAs found at very high levels in cancer cells and showed that they can trigger the release of active drug molecules into these cells, and not in healthy cells that do not contain the microRNAs.

Although this is an interesting find, there are some limitations to the study and much more work must be performed before treatments such as these can be used in patients. One key limitation is that this work was performed only in homogenous populations of either cancerous or healthy cells genetically engineered to be able to grow in plastic dishes. Therefore, similar experiments must be performed in animal models to show that this treatment can be tolerated and is effective in multi-organ systems with a mixture of cancerous and healthy cells, before even being considered for human trials.

Another consideration before this type of targeted treatment can be used in humans is the lack of clarity regarding the microRNA profile in healthy and diseased cells and tissues. Many diseases have dysregulated microRNA levels which must be investigated more fully, with a particular emphasis on the human disease profile, as this is often studied in model organisms which are not necessarily applicable to humans. This includes hepatitis C and other viral infections, heart attacks and heart failure, and metabolic diseases such as diabetes. It must be confirmed that the trigger microRNAs are only found in the target diseased cells, as the higher dosages that this type of targeted treatment would use may also effectively destroy whole populations of healthy cells that are unaffected by the lower dosages currently used in normal drug administration.

Written by Susanna Riley and edited by Ailie McWhinnie.

Susanna Riley is a third year PhD student in Tissue Repair and Regeneration. Find her on Twitter @SusannaERiley and LinkedIn @Susanna Riley.

Leave a Reply

Your email address will not be published. Required fields are marked *