Training action

The use of nanoparticles in health has increased particularly in recent years. Nano-objects are associated with organic molecules to "vectorize" drugs (chemotherapy, anti-inflammatory ...). The objective is then to concentrate these treatments on the pathological site by limiting the side effects. Nanoparticles are also used as contrast agents in medical imaging, especially in MRI or intrinsically as therapeutic agents. In the latter case, the nanoparticles, via physical phenomena emanating from their composition and / or their size, will, for example, lead to the destruction of cancer cells by phenomena of hyperthermia or radiosensitization. The French research community working in the field is vast and covers the fields of chemistry, physics, biology, medicine, process engineering and nanotechnology. However, locks remain to be lifted to bring more drug candidates, combining several modes of diagnosis and / or therapy, to the clinic. In particular, it is essential to define the important parameters that make it possible to envisage in vivo tests. The objective of this National Training Action is to highlight these locks to try to raise them in a concerted and interdisciplinary action.

Challenges

Many research teams and biotechnology companies have developed, for more than two decades, different types of nanoparticles for medical purposes. Of these, some have Marketing Authorization such as Myocet® (carrying doxorubicin) or Abraxane® (carrying taxol). At the preclinical level, several teams combine radiotherapy with nanoparticles of gold or with gadolinium or hafnium oxides or with lipid nanocapsules of ferrociphenol. 271 clinical studies implementing nanoparticles have been conducted to date (representing, since 2014, an increase of 19% each year). 60 are currently recruiting (nine in France). The results of these studies, in vivo, are promising. Since each nanoparticle has its own peculiarities (bioavailability, more or less important grafting capacity, internalization, etc.) it is however essential to develop new types or improve the properties of existing ones. The scientific community, in connection with the industrial world, must then confront the problems of scale-up, reproducibility and qualification of the batches produced.

The biodistribution and elimination of nanoparticles by different natural pathways depends on many factors including the size of nanoparticle agglomerates, their surface charge, their protein ring, and so on. All these parameters must be mastered and interactions with the living world better understood (role of their protein ring, role of vesicles once internalized nanoparticles etc.). These essential aspects to the development of new drug candidates will be a strong point of this training action with a reflection on the pre-in vivo tests.

The regulatory aspects in the field of health are essential, thus, the parameters to be controlled to control the different forms of toxicity of the nanoparticles will also be treated as well as the GMP standards to be implemented during the development of clinical batches.

Objectives

Thanks to the presence of experts from the field (stakeholders), the objective is to enlighten the scientific community on the locks to be lifted to facilitate the transfer of nanomedicine candidates from chemistry / physics laboratories to clinical studies (studies on cohorts of patients).

The aim is to guide the research of the French community on the work to remove its locks by focusing efforts on the most promising leads: what methods of syntheses to retain to ensure reproducibility and control of nanoparticles, what compositions and modes how to improve the biodistribution / elimination of nanoparticles, which biological tests to put in place, etc.

The objective is also to enable the different actors to better understand the French panorama of skills and possible collaborations in the field of nanomedicine in order to initiate later structuring projects (GDR, ANR, Europe, etc.).

Goal

At the end of the training trainees will be able to:

• Cite the techniques of synthesis and purifications of nanoparticles most adapted to GMP standards and scale-up;
• Cite methods of analysis to privilege to control the reproducibility of the batches;
• Cite the compositions, formulations and modes of administration to be preferred or avoided to facilitate obtaining the necessary authorizations to start clinical trials or commercialize;
• Know the parameters impacting the intrinsic physical properties of nanoparticles in vitro and in vivo;
• Explain the notions of multimodal and theranostic nanoplateforms;
• To know the tools of nanoscale characterizations of nanoparticle / protein interactions;
• Understand the parameters to control (including protein corona) to control the different forms of toxicity of nanoparticles, their biodistribution and their elimination;
• Know the main tests of cytotoxicity and cellular internalisation;
• To understand the role of biological nanovesicles for the vectorization of nanomedicines.