Chemistry plays a vital role in health, both cognitively and therapeutically. Indeed, the mechanisms involved in many diseases involve hormones, proteins and receptors. Studying their chemical structure and reactivity leads to their understanding. Chemistry also provides therapeutic solutions by reasoning by analogy with mechanisms already known outside biological environments. Chelation therapy, which uses ligands as simulacra active ingredients or as receptor inhibitors or activators, is for example used in the treatment of mercury poisoning and is based on interactions observed and confirmed by chemical analysis.
Chimie ParisTech researchers are applying their scientific expertise to better address the health issues of tomorrow. Treating cancer, diagnosing diabetes, understanding premature birth phenomena, improving imaging techniques,... Our teams are exploring many societal issues that are on the collective mind of the general public.
Chemistry at the service of the design of new therapeutic molecules
Chemistry plays a major role in the synthesis and manufacture of treatments. It also plays a key role in their design, especially in the galenic method, which is concerned with the formulation of the drug, its form (capsule, cream, etc.) and the assimilation of the active ingredient by the body. Chemistry is also involved in the research of active ingredients, where it can help develop methodologies for the design and synthesis of active molecules. It then works with biology to test and validate candidate molecules. The combination of these two disciplines, combining research and development to in vivo tests, saves valuable time, knowing that the average time between the design of a treatment until it is made available on the market is between 7 to 12 years.
The Inorganic Chemical Biology (ICB) team, lead by Dr. Gilles Gasser, at Chimie ParisTech since October 2016, is developing and synthesizing metal complexes for medicinal and biological purposes with the hopes that one of these complexes will participate in a clinical trial, which is an essential step in order to put a treatment on the market.
Cancer, the leading cause of death in developed countries and responsible for 13% of all deaths worldwide, is at the heart of the team’s research. The team is exploring active molecules’ action mechanisms, as well as the design of new complexes based on ruthenium, instead of platinum, to target tumor cells with more precision in order to reduce these treatments’ often significant side effects.
This team is also interested in another extremely promising therapeutic approach: photodynamic therapy (PDT). PDT activates metal complexes previously injected into the body that would otherwise remain inert using light radiation. These photosensitive complexes can then destroy the cells that are close to the area in which they have been activated, which can be used to target tumors more directly while limiting side effects. The effectiveness of these complexes depends on the presence of oxygen, which is rare in cancer cells as they are known to be hypoxic. The team is therefore considering the use of photoactivated chemotherapy (PACT), which uses specific complexes surrounded by a structure that changes shape when it comes in contact with light radiation, which can then be used in a low oxygen environment.
The team’s research also focuses on parasitic diseases, such as schistosomiasis (also known as bilharzia), a real public health problem: the WHO estimates that at least 206.5 million people needed treatment in 2016. Gilles Gasser and his team are studying how to integrate metal-based complexes into pre-existing organic molecules. This is not the first time that such a concept has been explored at school. Indeed the team led by Professor Jaouen was the first to successfully use this concept ever since the anticancer compound discovered was currently in the preclinical phase.
Chemistry not only contributes to the development of active principles for diseases with globally known mechanisms, but it also helps understand the action of treatments in order to optimize them. Using advanced analysis methods, chemistry is also used to access the mechanism of pathologies in order to design appropriate treatments.
Understanding how disorders work to come up with a cure: chemistry as a means of medical investigation
Analytical chemistry is used to develop and optimize techniques for the detection and quantification of compounds. These compounds that need to be analyzed are found in diverse and sometimes very complex media (called matrices) in the middle of many other molecules. Due to the difficulty of collecting large quantities and conserving them, biological matrices, such as blood or placenta, are characterized by an even greater complexity in this field. However, the study of such environments, especially when trying to understand the development of pathologies, may be essential to identify their warning signs and to subsequently find appropriate remedies to treat them.
Chimie ParisTech’s Synthèse, Electrochimie, Imagerie et Systèmes Analytiques pour le Diagnostic (SEISAD) team, led by Anne Varenne, studies the steps needed to make a diagnosis; it explores the synthesis of protein activity modulators, the development of new separation methods applied to healthcare, or even the development of new imaging techniques. It relies on analytical methods.
The team is also studying miscarriages and premature births, the number of which has increased dramatically in recent years. Its focus is on developing analytical devices for assessing oxidative stress in collaboration with the Prem’Up Foundation, supported by the Institut Pierre Gilles de Gennes pour la Microfluidique (IPGG). Although studies have shown that a change in the placenta’s oxygen level after three months of pregnancy would play a key role in this phenomenon, the mechanism involved remains misunderstood. SEISAD is developing a sensor to measure this oxidative stress, which can be assessed by measuring the concentration of superoxide anions, which results from this oxidative stress. The difficulty lies in adapting it to the placenta. In collaboration with ENS’ Electrochemistry team and using an animal model developed by INRA, SEISAD is trying to identify the mechanisms that lead to this oxidative stress (such as air pollution) and its impact on premature births or miscarriages.
Detecting diseases and improving imaging techniques: chemistry at the service of medical analysis
Whether dedicated to the study of tissues and organs, the detection of infectious lesions, tumors or herniated discs, there are many different types of imaging techniques. Contrast agents are sometimes used to improve image quality. Developing these agents has many challenges: their performance must go hand in hand with their biocompatibility and their stability in a biological environment. SEISAD is designing these agents in partnership with teams of biologists, then tests them on animal with inflammations or tumors. This team is particularly interested in the coupling of MRI imaging with near-infrared optical imaging in order to an additional method.
Contrast agents are also developed for PET (Positron Emission Tomography) imaging, which is used to observe cellular metabolism. Depending on the nature of the contrast agents, the biological targets will be different: observation of hormonal receptors, location of areas with hypoxic processes, etc.
Gilles Gasser’s team is developing new agents for PET based on the 89Zr isotope whose half-life is ideal for “radiolabeling” antibodies that take a long time to reach tumors after injection. However, the chelator currently available on the market (DFO) is not stable enough and accumulates in the bones. In collaboration with Professor Thomas Mindt’s team of the Medical University of Vienna, in Austria, Gilles Gasser’s team recently discovered a much more powerful compound than the one currently on the market.
Using electrochemical methods, SEISAD, along with the Interface, Electrochemistry & Energy (I2E) team and the Impeto Medical Company, is contributing to the development and understanding of how to implement a non-invasive means of detecting diabetes from a patient’s sweat, instead of measuring glucose levels in the blood as it is currently being done.
New biomaterials for prosthetics
In collaboration with the industrial community, the IRCP’s Structural Metallurgy (MS) team is developing new high-performance metallic materials for biomedical applications. Long-term partnerships aim to bring new and innovative implants to the market, both in the field of endovascular prostheses (stents) and in the field of intra-bone dental implants. For example, the MS team is collaborating with Biotech Dental within a LABCOM, both on processes to develop “smart” implants (Functionally Graded Biomaterials) and on a new family of metallic materials (recently patented) combining improved biocompatibility with mechanical properties not yet achieved for biomedical alloys.
Outlook
This overview shows us how the research conducted at Chimie ParisTech can meet tomorrow’s major health challenges: advancing the treatment of diseases, furthering the understanding of pathologies such as miscarriages to prevent and cure them, or even improving and developing the detection of diseases.
Auteur : Quentin Bouteille
Engineering student at Chimie ParisTech - Class of 2019.
Glossary
Ferrocenyl (group)
Derived from ferrocene, the ferrocenyl group contains one Fe(II) linked to two cyclopentadienyl ligands.
Hypoxic
An adjective derived from the term hypoxia, refers to a medium that is poor in oxygen.
Schistosomiasis
A widespread parasitic disease.
Oxidative stress
Type of aggression of the constituents of the cell due to reactive oxygen species (ROS) and reactive nitrogen species (RNS).
