NANO4ALL is a MSCA joint doctoral network project that will provide high-quality training to 15 Ph.D. fellows in nanomedicines (NMs), coordinated by the University of Angers with a European consortium including the Universities of Paris Cité, Patras, Pavia, Liège and Porto. Currently, NMs are receiving great attention as they are expected to revolutionize health care with great potential to deliver personalized and effective therapies to treat different pathologies such as cancer, infection, cardiovascular, neurodegenerative, or metabolic diseases. So far, most NMs on the market have been designed for intravenous (IV) administration, despite the limitations of this route of administration (qualified team for administration with high cost for health insurance and risk for infection). Therefore, NANO4ALL aims to train excellent young researchers to highlight the interest of NMs, able to encapsulate drugs, for various routes of administration (oral, pulmonary, transdermal, etc.) other than the IV route, focusing on the lipid nanocarriers, to enlarge their clinical use. The main objective is to enhance the translational approach of NMs through the prism of excellent joint training proposing to each PhD fellow to explore one lipid nanoparticle formulation and one administration route. NANO4ALL ambition will be to offer PhD training to define meaningful NMs with specifications based on safety, efficacy, clinical performance, and public acceptance in connection with the non-academic sector. NANO4ALL will be opening up career prospects in the academic and non-academic world (SME, large companies) training a new generation of young researchers with transferable skills, creative potential, an entrepreneurial and innovative spirit, to meet the current and future challenges of NMs. Indeed, medicines from NMs will increase in the future (growth rate estimation of 12% per year) and it is necessary to train researchers who will be ready to develop these new products for wider healthcare. Moreover, according to the European Technology Platform of Nanomedicine, to capture the benefit of this growth and to generate employment, Europe has to face off strong competition from the U.S. and new emerging centers in Asia. With NANO4ALL, future researchers will be trained in these highly promising biotechnology areas, allowing Europe to become a world leader with a strong competitive edge in creating jobs and generating economic wealth. To meet these expectations, in addition to benefit from research training from 2 universities highly recognized in the topic, each PhD student will have the opportunity to join a non-academic organization during a 3-month secondment to have a comprehensive training program connected to the pharmaceutical world. Among all the PhD projects, 2 will focus on the perception of patients for NMs and for the route of administration used for medicine. So, NANO4ALL will offer excellent training with the expertise of specialists and researchers in Life Science as well as the Human and Social Sciences, from academic and non-academic organizations (companies, SMEs, patient associations, etc). These non-academic associated partners will be fully integrated into the project because they will participate in the global training but also in the governance and in recruitment. The MSREI project will enable to add new beneficiaries with expertise complementary to that of the partners currently envisaged, as well as non-academic organizations to consolidate our international, intersectoral, and interdisciplinary consortium before the November 2024 deadline.

Resistance to traditional antimicrobial therapies is a rapidly increasing problem that in a few years could make infections impossible to treat and bring the state of medical care back to the pre-antibiotic era from the beginning of the last century. Indeed, the extensive use of antimicrobials worldwide (such as antibiotics) during the last decades has led to the apparition of a growing multiresistance phenomenon. Hence, if the strategy of combating infections is not significantly changed in the coming years, the problems related to resistant bacteria will escalate even further. At the same time, medicine faces many technological shortcomings that the development of new therapeutic systems tries to overcome, as Drug Delivery Systems (DDS) which unmistakably took an important place in human therapeutics. As a result, development of new effective antimicrobial compounds and alternative treatments is now a real issue and an important part of the European action plan against the rising threats from antimicrobial resistance. During the last decades, DDS definitely revealed essential in human therapeutics. DDS are obtained by the effective encapsulation of drugs in carriers allowing a safe and efficient controlled delivery in the body. Therefore, it is necessary to develop formulation processes which are green, flexible and respectful of Good Manufacturing Practices. The project challenge is to develop a sustainable continuous process producing nanostructured calcium carbonate (nCC) and biocompatible particles for antimicrobials delivery as Antibiotics or Antimicrobial peptides (AMP). The project team expertise and its complementarity provide the capacity to cover all the necessary competences to develop such an innovative drug product. The innovation of the CarboMIC project is to develop the Galenic-on-chip concept leading to the production of carriers and allowing the integration of ex situ and in situ physicochemical characterization close to the final product. Moreover, the proposed approach will allow a fine control of the physicochemical characteristics of drug carriers (size, structure, surface properties, drug loading), depending on the geometry of the microreactor, thermodynamics and hydrodynamics of the process. Besides on longer terms thanks to the use of a microfluidic device, it could be expected an easy scale-up at industrial- scale of this innovative antimicrobial carrier production. In addition, this approach leads to the minimization of energy consumption and environmental impacts which is an important issue for industrial processes development. In this way, the eco-design methodology will be deployed far upstream during the development of the encapsulation process. Finally, full physicochemical and biological characterization of the Antimicrobial-nCC carriers will be carried out to tune their functionalities in order to improve their therapeutic potential on the infected site and to choose the local administration route which is the most suitable.

Ferrocifens have been demonstrated to display anticancer properties by an original mechanism dependent on redox properties and generation of active metabolites targeting mitochondrial enzymes. However, these molecules are highly insoluble in water, requiring a formulation stage before they can be in vivo administered: lipid nanocapsules (LNC) have already demonstrated their ability to successfully encapsulate various hydrophobic therapeutic agents, such as ferrocifens, and offer the option of surface modification, making it possible to adapt the pharmacological behavior of the nanocarrier. Recent studies have highlighted the positive impact of oxidative stress on chemosensitivity and prognosis of ovarian cancer patients. Therefore, ovarian adenocarcinomas are an excellent model for defining the impact of selected ferrocifen loaded LNC as new therapeutic strategy. NateMoc proposes a unique approach that brings together a consortium of three complementary research teams with the goal of obtaining a proof of concept of the preclinical efficacy of ferrocifen loaded LNC in ovarian cancer. The consortium displays all the necessary chemical, technological, biological and pharmacological expertise gathering (i) the MINT laboratory (Partner 1) labelized by both INSERM and CNRS that will coordinate the project, internationally recognized in pharmaceutical technology (especially in nanomedicines), where the first encapsulation of ferrocifens was performed, (ii) the small innovatory company, Feroscan (Partner 2), that holds the patent of ferrocifens and works on the design and mechanistic behavior of new molecules, based on initial work done at Chimie Paris Tech, (iii) the Preclinical Investigation Laboratory (LIP) (Partner 3) of the Translational Research Department of Institut Curie which has developed relevant animal cancer models and displays a recognized in vivo expertise in pharmacology. NanoMetOv main goal is to carry out tightly focused cutting-edge research strategy with significant implications for public health in near future. Indeed, NaTeMOc aims at providing the proof of concept establishing the benefit of applying salient pro-oxidative drugs via original nanomedicine for treatment of ovarian cancer patients. This project will also provide an important cognitive value, both at Chemistry/Nanomedicine and Biology levels, through the synthesis of innovative chemical compounds, their formulation into active targeting nanocarriers and the study of a novel cancer metabolism deregulation.

Hyperbranched polymers (HBPs) are highly branched macromolecules. In comparison with linear polymers, they have several advantages including an internal cavity and abundant functional groups with multivalent effect. HBP structures are irregular in comparison with dendrimers ones but offer advantages in terms of facile synthesis in one-pot reaction, low cost-efficient synthesis and flexible compositions. Among the various synthetic strategies to target HBPs, self-condensing vinyl polymerization (SCVP) is considered one of the most versatile because it employs vinyl monomers that can be polymerized via radical chemistry tolerant with a wide range of chemical functions. SCVP combined to reversible addition-fragmentation chain transfer polymerization (RAFT) can be employed under soft conditions (water, room temperature), using functional monomers including cationic monomers, and therefore offers access to a variety of HBP structures. Despite their easy synthesis, HBPs are known to have a poor structural control and are limited to one kind of functional terminal groups. To tackle this limitation, the innovation of HBP-MultiReact project is to design and to synthesize structurally controlled HBPs with a variety of multiple reactive terminal groups through the combination of RAFT-SCVP in confined environments to structurally control the HBP cavity with a powerful chemical handle (azlactone derivatives) to target HBP with multiple chemoselective reactive functions at the periphery. The azlactone chemistry has emerged as a powerful chemical handle for the synthesis of a wide library of functional linear polymers. The advantages of the azlactone group are a high reactivity towards amines in mild conditions with a total atom economy. In this project, the “click” amine-azlactone reaction is expected to enable HBP periphery with a variety of multiple reactive terminal groups. In addition, conducting RAFT-SCVP in confined environment may favor a tunable structure of HBP cavity thanks to the physical confinement of the growing radicals to regulate the polymer–polymer coupling reactions. Such physical confinement is reached through the compartmentalization of reactants within nanodomains, by relying on polymerization in aqueous dispersed media. The ability of final cationic HBPs with multiple reactive terminal groups to conjugate targeting peptides and a therapeutic siRNA for preventing endothelium dysfunction associated with diabetes is assessed in this project. To achieve the aims of this challenging HBP-MultiReact project, three partners (IMMM-Le Mans, CP2M-Villeurbanne and MINT-Angers) will combine their complementary expertise in: i) the azlactone chemistry, ii) polymer synthesis in dispersed media, and iii) nanomedicine and cardiovascular disease.