Course Description

A. Sustainable polymers for the benefit of the society

Polymers and plastics are part of our dayly lifes. The aim of this course is to better understand the macromolecular science and how its use can benefit the whole society. In the introduction part the basic concepts of polymeric materials will be presented such as synthetic methods, characterization techniques and structure-properties relationship. In the next part of the course the environmental issues regarding to polymer industry and the omnipresence of plastics will be discussed.

First, bio-derived polymers will be presented. Emphasis will be given on a few industrially-produced and commercially-available bio-sourced polymers, such as poly(lactic acid), polyamide 11, polyhydroxyalkanoate, bio-based polyethylene or polybutylene adipate terephthalate.

The next part of this course will present the two main strategies that are currently intensively investigated in order to develop chemically recyclable plastics that would allow us to move towards a virtuous circular economy: repurposing and depolymerization processes.
Finally, an introduction about the various utilization of polymers as biomaterials and how they have greatly impacted the advancement of modern medicine will be discussed. In a following part, the recent progress in multifunctional delivery agents based on the tailored synthesis of polymers for gene therapy will be presented. In the last part, the course will cover the natural and synthetic polymers that are used in biomedical devices, such as prosthetic applications.

  1. Introduction to polymer science
    This first course serves to introduce the basic concepts of macromolecular science. The course will begin by defining what a monomer, a macromolecule, and a polymeric material are. Then, the mechanical and thermal properties will be discussed together with the characterization techniques. The importance of structure-properties relationships will be emphasized. In a second part, the classical methods of macromolecular synthesis will be discussed: step-growth, radical, and ionic polymerizations.
  2. Environmental issues related to polymer industry
    The first part of this course will focus on the plastics industry, including both (petro)chemical industry and plastics engineering. The polymers of major economic importance (“Big six”: polyethylene, polypropylene, polystyrene, poly(vinyl chloride), and poly(ethylene terephthalate)) will be presented.
    Their main application fields, such as packaging, building and construction or transportation, will be discussed.
    In the second part of the course, the focus will be put on environmental issues related to the manufacture, the use and end-of-life of plastics. The rapid increase of the global plastic production will be presented together with the depletion of oil resources. The necessity to develop bio-based alternatives to petro-based plastics will be discussed. Then, the pollution and health scandals caused by plastics materials will be analyzed: toxicity of additives, microplastics, marine plastic pollution, soil contaminations by non-biodegradable materials… In particular, the various end-of-life management options (mechanical or chemical recycling, energy recovery, landfill) will be discussed.
  3. Bio-based polymers
    Bio-based polymers are defined as materials for which at least a portion of the polymer consists of material produced from renewable resources, such as algae, bacteria, microorganisms, plants, etc.).
    The different synthesis strategies to obtain bio-sourced polymers will be presented. Natural polymers, such as polysaccharides, are known and extensively used for centuries. Several artificial polymers, which are obtained by the chemical modification of natural polymers, have been developed in the 19th century. Few polymers are formed directly as polymers in bio-organisms, such as bacteria. More recently, a substantial amount of research has been performed on the preparation of bio-based monomers allowing to obtain after polymerization structures similar to pre-existing petroleum-based polymers or fully original macromolecular structures. In particular, several biomass-derived platform chemicals have been developed and are very promising in the field of polymer synthesis. Particular emphasis will be placed on the few industrially-produced and commercially-available bio-sourced polymers, such as poly(lactic acid), polyamide 11, polyhydroxyalkanoate, bio-based polyethylene or polybutylene adipate terephthalate (PBAT). If the bio-based polymers are sources of hope and are seen as potential middle-term replacement to petroleum-based polymers, they still represent only 1% of the global plastic production. In addition, the generalization of bio-sourcing faces several major challenges, such as the availability of the resource, the cost of the new materials, the competition with food supply, or the pollution generated by the crops (fertilizers, herbicides…).
  4.  (Bio)degradable / depolymerizable polymers
    Plastic materials end of life is also a crucial issue. Different situations have to be considered. If polymers end up in the environment, as for example polymers found in cosmetics and detergents, or microplastics coming from paints, coating, tires and washing of textiles. For these applications, no waste collect is possible, and the polymers end up in wastewater and in waterways. The question of their accumulation in the environment has therefore become crucial and the use of biodegradable polymers is a priority. In this course, the question of the definition of biodegradability and its evaluation will first be addressed. Then the focus will be put on the biodegradable plastics, which are currently on the market and on their main applications. Finally, this course plans to provide an overview of the most promising current research.
    If it is possible to collect the waste, plastics are currently recovered energetically, recycled mechanically or landfilled. In many countries, energy recovery is the main outlet for waste. Nevertheless, this recovery generates atmospheric pollution and the production of so-called ultimate waste. The physical (mechanical) recycling of polymers is strongly promoted by public authorities. However, it also suffers from several important disadvantages such as the inevitable loss of quality of the recycled materials due to the degradation of the polymer chains and to the contamination by the accumulation of additives. In addition, the degradation of biodegradable polymers in landfills or directly in ecosystems leads to a loss of valuable materials and is therefore not the most interesting strategy from an economic point of view. Moreover, the accumulation of degradation products in the environment could eventually have harmful consequences. A growing number of studies are interested in the development of chemically recyclable plastics that would allow us to move towards a virtuous circular economy. The second part of this course will present the two main strategies that have been developed: repurposing and depolymerization processes.
    Repurposing consists of breaking down polymer chains by adjusting the pH or in the presence of a chemical reagent in order to convert them into new “building blocks” that can be used to synthesize new virgin materials with high added value.
    Depolymerization processes put forward a cycle of polymerization-depolymerization allowing to regenerate the original pure monomer and thus to re-synthesize a virgin polymer having its native properties.
    5. Biocompatible polymers for biomedical applications
    Introduction about the various utilization of polymers as biomaterials and how they have greatly impacted the advancement of modern medicine.
    The first part will be devoted to polymeric nano-systems for drug delivery. Stimuli-responsive polymeric systems (e.g. polymersomes or micelles) allow in particular the encapsulation, the delivery and the controlled release of hydrophobic or hydrophilic active ingredients. Current systems also often have targeting functions. An overview will also be given on the polymer prodrug strategies with their advantages (higher bioavailability and reduction of the side effects) and shortages. The importance of polymer-peptides conjugates will also be highlighted.
    In a second part, the recent progress in multifunctional delivery agents based on the tailored synthesis of polymers for gene therapy.
    In the last part, the course will cover the natural and synthetic polymers that are used in biomedical devices, such as prosthetic applications (e.g. stent, catheters, artificial skins, cartilage scaffolds). In particular, biodegradable macromolecular biomaterials provide the significant advantage of being able to be broken down and removed after they have served their function. Therefore, they can be used clinically as surgical sutures or as and implants. A wide range of natural and synthetic degradable polymers has been investigated for biomedical applications with novel materials constantly being developed in order to fit the required physical, chemical, biological, biomechanical and degradation properties.

 

B. Hybrid nanomaterials for biomedical and environmental applications

The objective of this course is to have an overview of existing hybrid nanomaterials, composed of both inorganic (silica, gold, magnetic) and organic (polymer) components and how they have recently been examined as promising platforms for biomedical applications. Moreover, we will see how hybrid nanomaterials can be developed for environmental applications.

Nanomaterials have received an increasing amount of attention for imaging and therapeutic applications over the past 20 years. They exhibit several advantages, including tunable size, high agent loading, tailorable surface properties, controllable or stimuli-responsive drug release kinetics, improved pharmacokinetics, and biocompatibility. Nanoparticles can be specifically targeted to certain regions of the body by conjugation with targeting ligands. They can also be engineered for imaging and therapeutic.

Quantum dots (QDs), display unique optical properties. As a result, they have been evaluated extensively for use as optical imaging probes both in vitro and in vivo.

Purely organic nanoparticles have also found widespread use as imaging and therapeutic agents.

Hybrid nanoparticles are composed of both inorganic and organic components that possess the beneficial features of both inorganic and organic nanomaterials, but also possess unique advantages over the other two types.

We will cover mostly two major classes of hybrid nanomaterials, namely gold-based nanomaterials and magnetic-based nanomaterials. Iron oxide nanoparticles have been used as contrast agents for magnetic resonance imaging (MRI). Gold nanoparticles with controllable morphologies have been extensively used for biological imaging applications as they can be engineered to exhibit strong absorption in the NIR region. We will see how the inorganic core are synthesized, their properties, how we can combine them to polymer and finally how they are used in biomedical applications.

Finally, we will see how magnetic nano composites can be used for environmental applications for water, soil and air treatment.

  1. Advanced functional nanomaterials

An introduction of nanomaterials and especially functional nanomaterials will be conducted. Aspects on their synthesis will be thoroughly covered, while emphasis will be given to their important functional properties. Current knowledge and future perspectives of their use in biomedical applications will also be covered

  1. Hybrid molecularly imprinted polymer for cancer applications

I-             All the aspects and generalities in cancer will be tought. More specifically, current definition of cancer, cancer’s development, diagnostic and treatments will be thoroughly covered, along with future perspectives in all these cancer related aspects.

II-            The synthesis and properties of Molecularly Imprinted Polymers (MIPs) will also be taught, while their usual applications will also be thoroughly evaluated

III-          Emphasis will be given to the use of MIP in cancer. More specifically, The use of MIPs in targeting, drug delivery and imaging in cancer will be thoroughly duscussed

  1. Magnetic nanoparticles and nanocomposites for environmental applications

– An Introduction in the uses of Magnetic nanoparticles and nanocomposites for environmental applications will be conducted. Specific paradigms of such applications will be outlined, For example, magnetically-assisted separation in water treatment and different separation technologies will be covered, while the coagulation-flocculation-sedimentation processes and their use in water treatment will be described, along with an overall definition of the Sirofloc Process and the Flocculation and magnetically-assisted sedimentation processes with maghemite nanoparticles. Moreover, several adsorption processes will also be outlined, including Description of the method – Application in water treatment, Carbon and graphene-based magnetic adsorbents, Magnetic hybrid silicas for heavy metal removal and Magnetic nanocomposite polymers and biopolymers and their use as adsorbents. The Advanced oxidation catalytic processes and other catalytic processes will also be discussed, with a Presentation of the processes and their potential use in water treatment, the use of Iron oxide/TiO2 nanocomposites as magnetic heterogeneous photocatalysts, and the Magnetic nanoparticles and magnetic /silica nanocomposites as heterogeneous Fenton catalysts. Other environmental applications of Magnetically activated water-treatment processes will also be outlined, such as Soil and air treatment, along with Sensing and other analytical processes

  1. Environmental applications of magnetic nanocomposites and molecularly imprinted polymers

With respect to the Environmental applications of magnetic nanocomposites and molecularly imprinted polymers, an outline of the Dispersive solid phase extraction experiments will be conducted, along with specific Absorption-desorption study(-ies), and an evaluation of the extraction efficiency, and validation of the overall method(s) applied.

 

It is well-known that many of pharmaceuticals and personal care products (PPCPs) are sufficiently eliminated during conventional wastewater, ending up into the environment either as unaltered parent compounds or as transformation products (TPs). The consumption of drugs is estimated at tones/year and is unfortunately increasing rapidly every year. The objective of this short course is to summarize the current status and future perspectives on the application of novel, magnetic nanocomposites and molecularly imprinted polymers for the efficient extraction and analysis of PPCPs from environmental matrices, as well as to study the crucial factors involved in the method validation when developing such extraction methods.

Figure 1. Schematic output of course

Specific objectives of the study are the extraction efficiency of the target compounds from the magnetic nanoparticles / MIPs as well as the setting of the multivariate optimization of the factors affecting the extraction efficiency using novel materials. In addition, it is noteworthy to study the lifetime and reusability of the materials and of course set the validation criteria based on Eurachem guidelines and criteria according to EN ISO/IEC 17025.

  1. Practical work (lab course) on adsorption processes (Synthesis of nanomaterials Characterization techniques, Application to batch adsorption experiments)

The attendees start the practical work in the Lab. They will be familiar with the separation process of adsorption through a brief synthesis of new bionanoadsorbent materials. Then, they will characterize these materials with majorly Scanning Electron Microscopy and FTIR spectroscopy. The evaluation of the adsorption effectiveness of the prepared bionanomaterials will be studied by carrying out brief adsorption experiments (i.e. by varying the contact time, pH, initial concentration) and making the appropriate calculations for the final evaluation.

 

C. Molecular chemistry for biomedical applications

The objective of this course is an overview of the design and synthesis of organic molecules, biomacromolecules and metal complexes as drugs. Moreover, the valorization of bioactives from sustainable natural sources as ingredients for the design and production of high value bio-functional medicinal products will be discussed. This section will be focused on the preparation and use of molecules in biomedical applications. The course is divided in six parts. In the first part the synthesis of heterocyclic molecules and their use as medicines will be discussed. The second part will outline the current status and future perspectives on the valorization of bioactives from sustainable natural sources as ingredients for the design and production of high value bio-functional medicinal products, including supplements, nutraceuticals and drugs. The third part will be focused on the biomacromolecules for therapy. The last three last parts will present the synthesis of metal complexes and their use in therapy and diagnostic. The very last part of the course will provide a comprehensive understanding of the role of porphyrins in photodynamic cancer therapy, including their chemistry, mechanism of action, clinical applications, and current research developments, following a practical lab work of porphyrin synthesis.

  1. Organic and medicinal chemistry in drug design

The first course will outline the top reactions used in drug discovery: toolbox of medicinal chemists. Then, an overview of heterocycle synthesis in drugs will be presented. We will be focused on top selling drug containing 5- and 6-membered ring nitrogen heterocycle. In addition, the strategies in drug discovery will be discussed and hit to lead optimization with case studies. In one of the cases studies, we will present small molecule as therapeutics for Alzheimer’s disease.

  1. Organic Bioactives from sustainable natural sources for the production of high value bio-functional products with anti-inflammatory and antithrombotic health promoting effects against chronic disorders, including cancer

The objective of this course is to outline the current status and future perspectives on the valorization of bioactives from sustainable natural sources as ingredients for the design and production of high value bio-functional medicinal products, including supplements, nutraceuticals and drugs, with promising anti-inflammatory and antithrombotic health promoting effects, against inflammation-related chronic disorders, such as cardiovascular diseases (CVD), cancer and metastatic manifestations, Neurodegenerative and renal disorders, autoimmune diseases and allergies, persistent infections and associated inflammatory manifestations, etc. (Figure 1).

Figure 1. Schematic output of course

The valorization of bioactives from sustainable natural sources as ingredients for the development of novel medicinal products with health promoting effects has received increased attention over the last two decades. Emphasis has been given to those sustainable sources (i.e. food industry by-products, cultured microorganisms of biotechnological and agro-food interest, etc) that are rich in natural bioactives, which can be recovered and valorized with the higher safety, efficacy and bioavailability-biodigestibility. This course is concerned with developing the students an understanding of the isolation, molecular characterization, structural elucidation and the biochemical/biological evaluation of structure activity relationships and potential synergism(s) of macro-/micro- bioactives from such sustainable natural sources, against inflammatory and thrombotic bio-molecular pathways and cell/tissue/organ biological responses, in vitro, ex vivo and in vivo, which is of paramount importance to assess structure-activity and causality. The recovery and valorization of characteristic active biomolecules from such sources will be outlined, including vitamins, bio-functional phenolics, lipid bioactives and functional fibers, along with several other bioactives, with specific medicinal properties in all aspects of targeting inflammation related chronic disorders

Finaly, through specific case studies we will see the current status and future perspectives on the valorization of Food Industry by-products as a characteristic example of sustainable natural sources that have a rich content of several of these bioactives, which can be utilized as ingredients in tailored medicinal products with anti-inflammatory and antithrombotic health benefits, against the aforementioned chronic disorders.

  1. Biomacromolecules for therapy

The first part of the course will be devoted to antibodies, more specifically to antibody-drug conjugates (ADC). In the second part the nucleic acids and gene therapy will be presented. Subsequently, biorthogonal chemistry for drug delivery. Finally, a Case study: development of an ADC for breast cancer treatment will be discussed.

  1. Metal based complexes in medicine

In this course an introduction on metal-based complexes present in medicine will be presented and then it will be focused on metal complexes for therapy and diagnostic. A case study: anticancer agents containing transition metal complexes will be discussed.

  1. Mechanistic investigations

The course will start with the methodologies for metal-based complexes speciation in cells. Then the tools for metal complexes intracellular localization will be addressed as well as the tools for targets identification.

  1. Porphyrins for photodynamic cancer therapy

Photodynamic therapy (PDT) is a treatment that aims to inactivate cells, microorganisms, or molecules through an oxidative reaction produced by irradiating a photosensitizing agent with a light of an appropriate resonant wavelength. The photosensitizer transfers energy from light to molecular oxygen, to generate reactive oxygen species (ROS), particularly the singlet oxygen (1O2). These reactive species induce a series of biological reactions that lead to cell death. The biological responses to the photosensitizer are activated only in the particular areas that have been exposed to light. The outcomes of PDT depend on the nature of the cells, as well as on the properties and localization of the photosensitizer and the illumination conditions. PDT is a promising modality for treatment of skin, esophageal, and lung cancers, as well as other non-neoplastic diseases such as atherosclerosis, macular degeneration, and rheumatoid arthritis. In the last century, extensive research has been carried out in basic and clinical area using PDT and two Nobel prizes were awarded in the field of PDT (N.R. Finsen, Phototherapy 1903 & H. Fischer, Examination of porphyrins 1929).

Figure 1.  Mechanism of action of photodynamic therapy (PDT).  PDT requires three elements: light, a photosensitizer and oxygen. When the photosensitizer is exposed to specific wavelengths of light, it becomes activated from a ground to an excited state. As it returns to the ground state, it releases energy, which is transferred to oxygen to generate reactive oxygen species (ROS), such as singlet oxygen and free radicals. These ROS mediate cellular toxicity.

The most extensively studied photosensitizers so far are porphyrins, consisting of tetrapyrrole bridged with four methylene groups. Porphyrins are one of invaluable and ubiquitous molecular species, which play critical roles in living systems including photosynthesis. The stable macrocyclic arrangement of porphyrin core forms an ideal anchoring site for metal atoms complexation. In addition, various derivatives can be obtained via introducing different substituents at the pyrrolic meso- or β-positions. Although the structure of porphyrins was suggested more than one hundred years ago, the studies of their synthesis, assemblies and applications have always been of great interest in the scientific community. This course aims to provide a comprehensive understanding of the role of porphyrins in photodynamic cancer therapy, including their chemistry, mechanism of action, clinical applications, and current research developments. The course will cover the basic principles of photodynamic therapy and will give historical perspective and evolution of PDT. Then the porphyrin synthesis will be described as well as the structural modifications of the photosensitizers for PDT. Next, the photocatalytic mechanism will be explained concerning the formation of ROS species. All recent advances of research will be discussed and future directions and challenges will be stated. Finally, the students will be able to synthesize a PDT porphyrin molecule in the laboratory.