Gold and silver chemistry: targeted therapies to treat cancer

In the fight against cancer, chemotherapy remains the most used treatment despite its side effects and its ineffectiveness against some types of tumors. The Gold and Silver Chemistry research group of the Institute of Chemical Synthesis and Homogeneous Catalysis (CSIC-University of Zaragoza) is working on the design of new targeted therapies for cancer treatment, trying to minimize side effects and improving effectiveness.

A first approach we are working on is tailored preparation of metal compounds that have specific selectivity towards several biological targets overexpressed in cancer cells. This would avoid the use of different drugs, while reducing side effects.

Another way to continue advancing in the field of medicine is to know how drugs are distributed within the cell and how they interact with molecules such as DNA, proteins or enzymes. For it, Fluorescence microscopy is very useful, as it does not pose any risk to the patient. This technique requires that the drugs have suitable fluorescent properties that current drugs do not have. The design of new fluorescent drugs for use in both diagnosis and therapy (theragnostic agents) is another of our lines of research.

Finally, the union in a single molecule of an antibody and a drug It will concentrate the advantages of immunotherapy and chemotherapy in a more efficient way.

What is photodynamic therapy?

Photodynamic therapy has become an alternative strategy to conventional chemotherapy. This technique offers the possibility of controlling the action of the drug, since its toxicity only occurs when a certain radiation is applied, and the risk of developing resistance is reduced. 

This methodology is based on using harmless and biocompatible photosensitizers, which, after the application of radiation that is not harmful to the tissues, are capable of being transformed into a very powerful medicine. To do this, photosensitizing agents are needed that can absorb radiation at lower energies, in the infrared, which are more penetrating and would allow access to a greater number of tumors, beyond skin cancer. Our group proposes the use of metallic compounds as photosensitizing agents, instead of the typical porphyrin derivatives commonly used to combat skin cancer.

What are multitarget drugs?

Multitarget drugs are those in which A single drug is capable of acting against more than one therapeutic target at the same time.. One of the most common targets of many drugs, including cisplatin, is DNA. However, considering that DNA is found in all types of cells, including healthy ones, interaction with it causes high side effects. Thus, It is of interest to investigate other pharmacological targets based on specific proteins that are overexpressed in cancer cells or that are unique in these cells.. Among them are a large number of enzymes and metalloenzymes, which promote cell invasion and cancer metastasis or are involved in the regulation of oxidation processes in the cell, or responsible for regulating basic biological processes, such as growth and cell proliferation, cell cycle and apoptosis. With this idea, the design of metal complexes based on gold or organic molecules, capable of selectively inhibiting some of the aforementioned proteins, allows acting through more than one target. These multitarget drugs are expected to increase their anticancer properties, in addition to providing greater selectivity and causing fewer side effects.

What is a drug-bound antibody?

Immunotherapy is a type of cancer treatment that stimulates the body's natural defenses, with the purpose of fighting it. Normally, the immune system detects and destroys cancer cells, or at least prevents or slows the growth of many tumors. When immune cells, called tumor-infiltrating lymphocytes, are found in tumors, it is a sign that the immune system is responding to the tumor. Today, several types of immunotherapies are used to treat cancer, such as monoclonal antibodies, vaccines, T cells, etc. Antibody-drug conjugates represent promising therapeutic agents, combining cancer chemotherapy with immunotherapy. These conjugates potentially add the selectivity of antibodies to the antitumor potency of chemotherapeutic agents.