Postdoc in Organic / Medicinal Chemistry

Created in 2007, the Institute of Chemistry and Biology of Membranes and Nano-objects (CBMN) is a joint research unit of the CNRS (main INC, secondary INSB), the University of Bordeaux (Science and Technology Department for health) and the Institut National Polytechnique Bordeaux. The CBMN Institute is also associated with Bordeaux Science Agro. CBMN has around 200 persons (50% permanent and 50% non-permanent).

CBMN is a multidisciplinary institute and operates at the interface between Chemistry, Biology and Physics by hosting 16 research groups organized in four scientific domains:

• Chemical biology and Supramolecular chemistry (CBSC),
• Biomedical research: fundamental and translational (BioFAP),
• Multiscale Biophysics (MSB),
• Nutraceutical, Medical and Food applications of biomolecules (NMFAB).

Chemotherapy is one of the major alternative to fight cancer today. If, ideally, the use of a chemotherapeutic agent should selectively kill cancer cells, unfortunately they also affect healthy tissues, inducing severe side effects and toxicity to different body organs (liver, heart, kidneys, etc.). Nano-vehicles revealed as promising solutions to improve the bioavailability and the therapeutic index of existing drugs or to reduce the low attrition rates striking the pharma industry today. The phospholipids-derived carriers are highly promising because of their enhanced biocompatible profile. However, despite its early discovery more than 60 years ago, this type of “magic bullet” still needs to be improved, only 15 liposome-based delivery systems are used in clinics today. Conventional, stealth or targeted generations of liposomes tackled many delivery-related issues; however, solving the temporal constraint of the delivery process is still in its infancy: the nano-carrier should be able to release its target only on demand. The concept of stimuli-responsive liposomes emerged naturally from the need of controlling the cargo release. Among them, the exogenous-triggered systems have a better temporal control of the drug release and they are less prone to patients’ variation compared to endogenous stimuli (pH, hypoxia, etc.). Formulations designed to be triggered by external stimuli include ultrasound-, magnetic, thermo-, electric- or light-induced cargo release. Most of those require natural phospholipids, but also the use of additives that induce liposomal deteriorations in the presence of an external stimulus.

We are currently exploring an “additive-free” approach: photo-sensitive liposomes (PSL) build from photo-sensitive phospholipids (PSP). We already validated the proof of concept of such photo-sensitive liposomes: highly stable in the absence of irradiation but also highly permeable when stimulated by light. A patent was recently submitted in collaboration with SATT Aquitaine on this new methodology. This project is funded by the “Initiative of Excellence” – University of Bordeaux.

As the drug release profile is highly dependent on the phospholipids composing the nanoparticles, we are currently interested in developing a library of photosensitive phospholipids (PSPs). We intend to develop nano-delivery systems suitable for clinical applications in collaboration with the other partners of this project. These will be formulated and investigated for their ability to induce the desired cargo release. The design of the target PSPs is guided by molecular modelling studies (coarse-grained molecular dynamics to predict the self-assembling process and the properties of the generated nanoparticles). 

The recruited fellow will mainly work on the synthesis of a library of photosensitive phospholipids. This will involve multi-step synthesis and trivial methods from organic chemistry. He/she is expected to work in collaboration with formulation/analytical scientists and modellers and to participate to reports and scientific articles writing.

The experiments will be conducted at CBMN in the group of Prof. Isabelle Bestel and will be directly supervised by Dr. Edouard Badarau:

http://www.cbmn.u-bordeaux.fr/28-chimie-biophysique-modelisation-de-biomolecules-et-imagerie-numerique.html#trombinoscope

The recruited fellow must hold a PhD (in organic chemistry / medicinal chemistry / bioorganic chemistry or equivalent) and have less than 3 years of experience after the PhD defense.

Essential skills: multi-step synthesis on 10mg to 100g scale; air and moisture-sensitive chemistry. Previous experience in amphiphiles chemistry is not essential. The chemistry and methodologies in this project are similar to those published previously by the host group (e.g. Bioconjugate Chem. 2021, 32, 553−562).

Proficiency in scientific reports / articles writing is also essential.

A keen interest in chemistry at the interface organic chemistry / medicinal chemistry / nanomedicines is recommended.

The recruited fellow is expected to be trained in multi-step organic or/and medicinal chemistry. He will synthesize a library of photosensitive phospholipids with potential applications in nanomedicine.