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Persister cancer cells represent rare populations of cells resistant to therapy. Cancer cells can exploit epithelial-mesenchymal plasticity to adopt a drug-tolerant state that does not depend on genetic alterations. Small molecules that can interfere with cell plasticity or kill cells in a cell state-dependent manner are highly sought after. Salinomycin has been shown to kill cancer cells in the mesenchymal state by sequestering iron in lysosomes, taking advantage of the iron addiction of this cell state. Here, we report the chemo- and stereoselective synthesis of a series of structurally complex small molecule chimeras of salinomycin derivatives and the iron-reactive dihydroartemisinin. We show that these chimeras accumulate in lysosomes and can react with iron to release bioactive species, thereby inducing ferroptosis in drug-tolerant pancreatic cancer cells and biopsy-derived organoids of pancreatic ductal adenocarcinoma. This work paves the way toward the development of new cancer medicines acting through active ferroptosis.

As a continuation of our studies toward the development of small molecules to selectively target cancer stem cells (CSCs), a library of 18 novel derivatives of salinomycin (

Ferroptosis is a dedicated mode of cell death involving iron, reactive oxygen species and lipid peroxidation. Involved in processes such as glutathione metabolism, lysosomal iron retention or interference with lipid metabolism, leading either to activation or inhibition of ferroptosis. Given the implications of ferroptosis in diseases such as cancer, aging, Alzheimer and infectious diseases, new molecular mechanisms underlying ferroptosis and small molecules regulators that target those mechanisms have prompted a great deal of interest. Here, we discuss the current scenario of small molecules modulating ferroptosis and critically assess what is known about their mechanisms of action.

Ferroptosis is a dedicated mode of cell death involving iron, reactive oxygen species and lipid peroxidation. Involved in processes such as glutathione metabolism, lysosomal iron retention or interference with lipid metabolism, leading either to activation or inhibition of ferroptosis. Given the implications of ferroptosis in diseases such as cancer, aging, Alzheimer and infectious diseases, new molecular mechanisms underlying ferroptosis and small molecules regulators that target those mechanisms have prompted a great deal of interest. Here, we discuss the current scenario of small molecules modulating ferroptosis and critically assess what is known about their mechanisms of action.

Salinomycin (1) exhibits a large spectrum of biological activities including the capacity to selectively eradicate cancer stem cells (CSC), making it and its derivatives promising candidates for the development of drug leads against CSC. It has been previously shown that salinomycin and its C20-propargylamine derivative (Ironomycin (2)) accumulate in lysosomes and sequester iron in this organelle. Herein, a library of salinomycin derivatives is reported, including products of C20-amination, C1-esterification, C9-oxidation, and C28-dehydration. The biological activity of these compounds is evaluated against transformed human mammary epithelial HMLER CD24low /CD44high cells, a well-established model of breast CSC, and HMLER CD24high /CD44low cells deprived of CSC properties. Unlike other structural alterations, derivative 4, which displays a cyclopropylamine at position C20, showed a strikingly low IC50 value of 23 nm against HMLER CD24low /CD44high cells. This study provides highly selective molecules to target the CSC niche, a potential interesting advance for drug development to prevent cancer resistance.

Surgical management of peritoneal metastases raises the problem of the theoretical spread of the entire peritoneal surface. Intraperitoneal photodynamic therapy (IntraPDT) has been limited by the lack of specificity of photosensitizers (PS) and difficulties to bring light into the abdominal cavity. Recent data in ovarian cancer may give development opportunities for IntraPDT. Intraperitoneal PDT could be an option but the level of evidence of research in this topic must increase. Our opinion is that the most important is to have a realistic idea of what we can objectively expect from PDT and the feasibility of its daily application. At the time of personalized medicine, it is mandatory to select population eligible for a targeted PS administration and who could benefit from the process. The design of a specific PS for each subtype of cancers seems essential to avoid side effects on healthy tissue. On the contrary, our progress on lighting solutions can be beneficial for all patients with an indication of IntraPDT regardless of the origin of PM. A common lighting system developed for all cancers eligible for IntraPDT could be adapted with light source of specific wavelength to activate dedicated PS.

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2&ndash, 5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2&rsquo, s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

Photodynamic therapy is a therapeutic option to treat cancer and other diseases. PDT is used every day in dermatology, and recent developments in the treatment of glioblastoma, mesothelioma or prostate have demonstrated the efficacy of this modality. In order to improve the efficacy of PDT, different strategies are under development, such as the use of targeted PS or nanoparticles to improve selectivity and the design of light devices to better monitor the light dose. Due to the low penetration of light into tissue, another way to improve the efficacy of PDT to treat deep tumors is the use of upconversion NPs or bi-photon absorption compounds. These compounds can be excited in the red part of the spectrum. A relatively new approach, which we will call PDTX, is the use of X-rays instead of UV-visible light for deeper penetration into tissue. The principle of this technique will be described, and the state-of-art literature concerning this modality will be discussed. First, we will focus on various photosensitizers that have been used in combination with X-ray irradiation. To improve the efficacy of this modality, nanoparticles have been designed that allow the conversion of high-energy ionizing radiation into UV-visible light; these are potential candidates for the PDTX approach. They will be discussed at the end of this review.

This study describes the employment of gold nanorods (AuNRs), known for their good reputation in hyperthermia-based cancer therapy, in a hybrid combination of photosensitizers (PS) and peptides (PP). We report here, the design and the synthesis of this nanosystem and its application as a vehicle for the selective drug delivery and the efficient photodynamic therapy (PDT). AuNRs were functionalized by polyethylene glycol, phototoxic pyropheophorbide-a (Pyro) PS, and a &ldquo, KDKPPR&rdquo, peptide moiety to target neuropilin-1 receptor (NRP-1). The physicochemical characteristics of AuNRs, the synthesized peptide and the intermediate PP-PS conjugates were investigated. The photophysical properties of the hybrid AuNRs revealed that upon conjugation, the AuNRs acquired the characteristic properties of Pyro concerning the extension of the absorption profile and the capability to fluoresce (&Phi, f = 0.3) and emit singlet oxygen (&Phi, &Delta, = 0.4) when excited at 412 nm. Even after being conjugated onto the surface of the AuNRs, the molecular affinity of &ldquo, for NRP-1 was preserved. Under irradiation at 652 nm, in vitro assays were conducted on glioblastoma U87 cells incubated with different PS concentrations of free Pyro, intermediate PP-PS conjugate and hybrid AuNRs. The AuNRs showed no cytotoxicity in the absence of light even at high PS concentrations. However, they efficiently decreased the cell viability by 67% under light exposure. This nanosystem possesses good efficiency in PDT and an expected potential effect in a combined photodynamic/photothermal therapy guided by NIR fluorescence imaging of the tumors due to the presence of both the hyperthermic agent, AuNRs, and the fluorescent active phototoxic PS.

Resume Objectif Le pronostic des cancers epitheliaux de l’ovaire reste conditionne par la qualite de l’exerese chirurgicale. Un des principaux facteurs de reduction des recidives peritoneales est l’absence de residu macroscopique en fin d’intervention. L’association chirurgie–chimiotherapie ne previent pas toujours la survenue de ces recidives qui concernent 60 % des femmes en remission a l’issue de ce traitement. Parmi les hypotheses expliquant ce taux eleve de recidive, l’existence d’une maladie microscopique residuelle en fin chirurgie est evoquee. Notre objectif est de traiter par therapie photodynamique (PDT) les metastases peritoneales ignorees lors de la chirurgie. Le ciblage therapeutique est indispensable. Nous presentons ici les proprietes d’un photosensibilisateur couple a l’acide folique et ainsi dirige vers le recepteur au folate, surexprime par la majorite des CEO. Methode Le photosensibilisateur a ete teste in vitro sur lignees cellulaires et in vivo sur un modele animal de carcinose peritoneale pour l’evaluation de ses capacites a atteindre la cible tumorale, a emettre une fluorescence detectable, a induire la destruction du tissu cible. Resultats Nous avons montre la bonne specificite de la molecule pour sa cible. Les lignees cellulaires emettent une fluorescence detectable apres mise en culture dans un milieu enrichi en photosensibilisateur ce qui indique leur capacite a incorporer la molecule d’interet. Cette fluorescence a ete detectee in vivo au niveau des metastases peritoneales. La PDT permet d’obtenir la mort cellulaire des cellules humaines in vitro avec une bonne efficacite. Conclusion Un photosensibilisateur specifique pourrait autoriser le developpement d’une technique de PDT sure et efficace.

International audience; Self-aggregation of hydrophobic porphyrin-based photosensitizers (PSs) in aqueous biological environment decreases their bioavailability and in vivo therapeutic efficacy, which hampers their clinical use in photodynamic therapy (PDT). In the current study, we explore three new supramolecular systems based of hydrophobic PSs (i.e. 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) or 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (P1COOH)) non-covalently or covalently attached to β-CD. The two non-covalent solid inclusion complexes (β-CD)2/mTHPP and [(β-CD)/P1COOH]4 are prepared by a new co-precipitation@lyophilization combined method and the covalent conjugate β-CD-P1 by click chemistry. The binding type effect and effectiveness on the disaggregation in aqueous medium and in vitro PDT efficacy against glioblastoma cancer cells of PSs are investigated for the three β-CD/PS systems. The findings reveal a remarkable improvement of the disaggregation and in vitro PDT activity of these β-CD/PS systems compared to the free PSs, except for [(β-CD)/P1COOH]4 inclusion complex caused by J-type self-aggregation of the inclusion complex in tetrameric form. β-CD-P1 conjugate shows the higher in vitro PDT efficacy compared to the other β-CD/PS systems. Overall, the results indicate that the disaggregation in aqueous medium and in vitro PDT activity of hydrophobic PSs can be improved by their binding to β-CD and the covalent binding is the best approach.

Chemical Biology is the science of designing chemical tools to dissect and manipulate biology at different scales. It provides the fertile ground from which to address important problems of our society, such as human health and environment.

In this review, the use of dye-sensitized nanoparticles (NPs) for heterogeneous photocatalysis related to water purification is considered. The dye-sensitization by the mean of organic photosensitizers (PSs) appears as a relevant alternative method to enhance the photocatalytic efficiency and, particularly, to extend the activity towards visible light domain. The discussion covers the impact of several parameters on the photodegradation performances of various pollutants. Those factors include the type of NPs, the nature and the content of the PS, the linkage mode between the PS and the surface of the NPs (physisorption, covalent grafting), the presence of a heavy-metal atom coordinated to the ring of the PS, and the type of light used for the activation (UV, visible or solar). These processes have been conducted principally with TiO2 coupled with porphyrin or phthalocyanine. The main trends in terms of the effect of the PS nature, the linkage mode, the PS content, the nature of metallic heavy atoms are extracted by studying the photodegradation performance of the PS/TiO2 materials. In the research of alternative photocatalysts, PS/ZnO systems has been evaluated since ZnO shares many similarities with titania. Recent hybrid photocatalysts based on carbon materials such as PS/fullerene and PS/graphene are also discussed. For each system and under each irradiation source, the mechanism of the light-induced charge transfer and the nature of the radicals generated is also thoroughly described. When necessary, besides water treatment, other applications of the same photocatalysts are considered to illustrate some phenomena and mechanisms such as charge transfer and radicals nature.

International audience; The formation of imidazolones by means of dehydrative cyclization was developed, using bistrimethylsilylacetamide. This highly versatile, friendly, safe, and cost-effective reagent exhibited a very large scope of starting materials, since it can promote the formation of 4-benzylidene imidazolones, 4,4-dialkyl-imidazolones, bearing alkyl, aryl, or even no substituent at C2, the latter being unavailable by classical methods. This reagent also afforded clean and high-yielding one-pot reactions in the presence of amine or imine reagents.

Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS then reacts with molecular oxygen to produce reactive oxygen species (ROS), leading to cellular damage. One of the drawbacks of PSs is their lack of solubility in water and body tissue fluids, thereby causing low bioavailability, drug-delivery efficiency, therapeutic efficacy, and ROS production. To improve the water-solubility and/or drug delivery of PSs, using cyclodextrins (CDs) is an interesting strategy. This review describes the in vitro or/and in vivo use of natural and derived CDs to improve antitumoral PDT efficiency in aqueous media. To achieve these goals, three types of binding modes of PSs with CDs are developed: non-covalent CD–PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies. This review is divided into three parts: (1) non-covalent CD-PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies, (2) incorporating CD–PS systems into hybrid nanoparticles (NPs) using up-converting or other types of NPs, and (3) CDs with fullerenes as PSs.

Eloïse Thomas,1 Ludovic Colombeau,2 Mickaël Gries,3,4 Thibaut Peterlini,3,4 Clélia Mathieu,1 Noémie Thomas,3,4 Cédric Boura,3,4 Céline Frochot,2 Régis Vanderesse,5 François Lux,1 Muriel Barberi-Heyob,3,4 Olivier Tillement1 1Université Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), Institut Lumière Matière, Lyon, 2Laboratoire Réactions et Génie des Procédés, Université de Lorraine-CNRS, Nancy, 3Université de Lorraine, Research Center for Automatic Control of Nancy (CRAN), 4CNRS, CRAN, Vandœuvre-lès-Nancy, 5Laboratoire de Chimie Physique Macromoléculaire, Université de Lorraine-CNRS, Nancy, France Abstract: Despite combined treatments, glioblastoma outcome remains poor with frequent local recurrences, indicating that a more efficient and local therapy is needed. In this way, vascular-targeted photodynamic therapy (VTP) could help tumor eradication by destroying its neovessels. In this study, we designed a polysiloxane-based nanoparticle (NP) combining a magnetic resonance imaging (MRI) contrast agent, a photosensitizer (PS) and a new ligand peptide motif (KDKPPR) targeting neuropilin-1 (NRP-1), a receptor overexpressed by angiogenic endothelial cells of the tumor vasculature. This structure achieves the detection of the tumor tissue and its proliferating part by MRI analysis, followed by its treatment by VTP. The photophysical properties of the PS and the peptide affinity for NRP-1 recombinant protein were preserved after the functionalization of NPs. Cellular uptake of NPs by human umbilical vein endothelial cells (HUVEC) was increased twice compared to NPs without the KDKPPR peptide moiety or conjugated with a scramble peptide. NPs induced no cytotoxicity without light exposure but conferred a photocytotoxic effect to cells after photodynamic therapy (PDT). The invivo selectivity, evaluated using a skinfold chamber model in mice, confirms that the functionalized NPs with KDKPPR peptide moiety were localized in the tumor vessel wall. Keywords: nanoparticles, PDT, vascular targeting strategy, brain tumor, NRP-1, peptide ligand, MRI

International audience; In this study, light-sensitive photosensitizers (Chlorin e6, Ce6) were linked to TiO2 and SiO2 nanoparticles (NPs) in order to develop new kinds of NP-based drug delivery systems for cancer treatment by PDT. TiO2 or SiO2 NPs were modified either by the growth of a polysiloxane layer constituted of two silane reagents ((3-aminopropyl)triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS)) around the core (PEGylated NPs: TiO2@4Si-Ce6-PEG, SiO2@4Si-Ce6-PEG) or simply modified by APTES alone (APTES-modified NPs: TiO2-APTES-Ce6, SiO2-APTES-Ce6). Ce6 was covalently attached onto the modified TiO2 and SiO2 NPs via an amide bond. The absorption profile of the hybridized NPs was extended to the visible region of the light. The physicochemical properties of these NPs were explored by TEM, HR-TEM, XRD, FTIR and zeta potential. The photophysical characteristics including the light absorption, the fluorescence properties and the production reactive oxygen species (1O2 and HO) were also addressed. In vitro experiments on glioblastoma U87 cells were performed to evaluate the photodynamic efficiency of the new hybridized NPs. The cells were exposed to different concentrations of NPs and illuminated (λexc = 652 nm, fluence rate 10 J/cm2). In contrast to the PEGylated NPs, the APTES-modified nanosystems were found to be more efficient for PDT. An interesting photodynamic effect was observed in the case of TiO2-APTES-Ce6 NPs. After illumination, the viability of U87 was decreased by 89% when they were exposed to 200 μg/mL of TiO2-APTES-Ce6 NPs, which corresponds to 0.22 μM of Ce6. The same effect can be obtained with free photosensitizer but using a higher concentration of 10 μM of Ce6.

International audience; A new aminophosphonic acid was synthesized by condensation of 4,4'-(propane-2,2-diylbis(4,1-phenylene)bis(oxy)dianiline), phosphorous acid and formaldehyde, according to the Moedritzer-Irani reaction. The structure of the inhibitor was analyzed by 1H and 31P NMR, FT-IR, mass spectrometry and thermogravimetry.The new inhibitor presented high efficiency in a static condition on the model imitating water composition with respect to CaCO3 and CaSO4 deposits. The crystal formation of CaCO3 and CaSO4 was investigated by scanning electronic microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The inhibitor obviously affected the procedure of crystal growth. The morphology of the CaCO3 crystals, in the absence of inhibitor, showed a predominant content of rhombohedral crystals (calcite), whereas in the presence of inhibitor we could observe a mixture of calcite with acicular crystals (aragonite) and a small content of spherical crystals (vaterite). Concerning CaSO4 crystals, thin needles with a smooth surface were observed in the absence of the inhibitor, which became thicker with many crystal defects in the presence of the inhibitor.Consequently, the new aminophosphonic acid described here can be used as a potential scale inhibitor

In this study, light-sensitive photosensitizers are coupled to titanium dioxide and silicon dioxide nanoparticles in order to develop new kinds of visible light photocatalysts for water treatment applications. The influence of the mode of surface modification of the nanoparticles and the nature of the linked photosensitizer (PS) on the photocatalytic activity under visible and solar light was considered. The TiO2 Degussa P25 core was either coated with a polysiloxane layer formed by two silane reagents (3-aminopropyl tetraethoxysilane (APTES) and tetraethyl orthosilicate (TEOS)) emerging a core-shell nanosystem, or simply modified by APTES alone. In both systems, the APTES mediated the amide covalent linkage between the TiO2 and the PS. Monocarboxylic tetraphenyl porphyrin (P1-COOH) and chlorin e6 (Ce6) were used to sensitize the TiO2 semiconductor. Those photosensitizers serve as visible light antenna, thus modifying the UV-limited photoresponse properties of the hybridized TiO2 nanoparticles. The morphological and structural properties of the synthesized nanosystems were investigated through TEM, XRD, DLS, FTIR, zeta potential and UV–vis absorption. The photophysical properties (fluorescence emission and singlet oxygen formation) were also probed. The photodegradation of two model pollutants, methylene blue and methyl orange, was used to assess the photocatalytic efficiency of the prepared catalysts under simulated solar and pure visible lights. Similar sensitized nanosystems with a SiO2 core were also prepared and characterized in order to assess the contribution of the support in the photocatalytic degradation process. The reactive oxygen species involved in the photodegradation process were also studied.

Further improvements in Photodynamic therapy (PDT) necessitate that the dye targets more selectively tumour tissues or neovascularization than healthy cells. Different enzymes such as matrix metalloproteinases (MMPs) are overexpressed in tumour areas. Among these MMPs, gelatinases (MMP-2 and MMP-9) and its activator MMP-14 are known to play a key role in tumour angiogenesis and the growth of many cancers such as glioblastoma multiforme (GBM), an aggressive malignant tumour of the brain. These last years, the concept of photodynamic molecular beacons (PMB) became interesting for controlling the photosensitizer’s ability to generate singlet oxygen (1O2) close to target biomolecules as MMPs. We report herein novel PMBs triggered by MMP-2 and/or MMP-9 and/or MMP-14, comprising a photosensitizer and a singlet oxygen quencher linked by MMP cleavable peptide linker (H-GRIGFLRTAKGG-OH). First of all, we focused on the synthesis and the photophysical study of different derivatives photosensitizer-peptide. This preliminary work concluded on an influence of the nature and the distance from the peptide, but not of the position of the photosensitizer in these derivatives on the proteolytic enzymatic action. The nature of the quencher used (a blackberry quencher (BBQ-650) or a black hole quencher (BHQ3)) does not influence the enzymatic action. We also studied the influence of an additional PEG spacer. Finally, the synthesis, the singlet oxygen quenching efficiency and the enzymatic activation of these new MMP- cleavable-PMBs were compared.

International audience

International audience; In the present work, we describe a successful strategy centered on the use of click chemistry to synthesize mono-, di-and triporphyrin building blocks named [ZnTPP] 1 , [ZnTPP] 2 and [ZnTPP] 3. The number of photosensitizers (ZnTPP unit) coupled to the building blocks does not seem to dramatically modify the photophysical properties of the photosensitizer in terms of fluorescence and singlet oxygen formation, quantum yields and lifetime. These building blocks, obtained in high yield, could be combined with a targeting agent (vector) to create new photosensitizer-vector conjugates to investigate the optimum ratio of photosensitizer needed for maximum photodynamic therapy efficiency.

Recent researches in photodynamic therapy have focused on novel techniques to enhance tumour targeting of anticancer drugs and photosensitizers. Coupling a photosensitizer with folic acid could allow more effective targeting of folate receptors which are over-expressed on the surface of many tumour cells. In this study, different folic acid-OEG-conjugated photosensitizers were synthesized, characterized and their photophysical properties were evaluated. The introduction of an OEG does not significantly improve the hydrophilicity of the FA-porphyrin. All the FA-targeted photosensitizers present good to very good photophysical properties. The best one appears to be Ce6. Molar extinction coefficient, fluorescence and singlet oxygen quantum yields were determined and were compared to the corresponding photosensitizer alone.

International audience

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Presentation Poster PC-028; International audience

International audience; Folic acid is a small molecule, also known as vitamin B-9. It is an essential compound involved in important biochemical processes. It is widely used as a vector for targeted treatment and diagnosis especially in cancer therapeutics. Nevertheless, not many authors address the problem of folic acid degradation. Several researchers reported their observations concerning its denaturation, but they generally only took into account one parameter (pH, temperature, light or O-2 etc.). In this review, we will focus on five main parameters (assessed individually or in conjunction with one or several others) that have to be taken into account to avoid the degradation of folic acid: light, temperature, concentration, oxygen and pH, which are the most cited in the literature. Scrupulous bibliographic research enabled us to determine two additional degradation factors that are the influence of singlet oxygen and electron beam on folic acid stability, which are not considered as among the prime factors. Although these two factors are not commonly present as compared to the others, singlet oxygen and electron beams intervene in new therapeutic technologies and must be taken in consideration for further applications such photodynamic or X-rays therapies.

International audience; Among all photosensitive monomers reported in the literature, o-nitrobenzyl acrylate (NBA) was selected in this present study. Two strategies were compared to produce azido-terminated poly(o-nitrobenzyl acrylate) (PNBA) using controlled Single Electron Transfer-Living Radical Polymerization (SET-LRP). In a parallel way, dextran (Dex) was modified by the introduction of several alkynyl-terminated hydrophobic chains. Finally, an Huisgen-type Copper (I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) click-chemistry was carried out to produce amphiphilic Dex-g-PNBA glycopolymers with different number and length of PNBA grafts. 2D DOSY H-1 NMR was used to prove the formation of such glycopolymers. Preliminary study on Dex-g-PNBA self-assembly was done by measuring the critical water content (CWC) above which Dex-g-PNBA started to auto-organize themselves to produce nano-objects. Finally, under UV irradiation, PNBA grafts turn into poly(acrylic acid) ones giving light-sensitive properties to such amphiphilic Dex-g-PNBA. Such properties were evaluated and compared with those of PNBA.

International audience; Photodynamic therapy (PDT) is a well-established technique employed to treat aged macular degeneration and certain types of cancer, or to kill microbes by using a photoactivatable molecule (a photosensitizer, PS) combined with light of an appropriate wavelength and oxygen. Many PSs are used against cancer but none of them are highly specific. Moreover, most are hydrophobic, so are poorly soluble in aqueous media. To improve both the transportation of the compounds and the selectivity of the treatment, nanoparticles (NPs) have been designed. Thanks to their small size, these can accumulate in a tumor because of the well-known enhanced permeability effect. By changing the composition of the nanoparticles it is also possible to achieve other goals, such as (1) targeting receptors that are over-expressed on tumoral cells or neovessels, (2) making them able to absorb two photons (upconversion or biphoton), and (3) improving singlet oxygen generation by the surface plasmon resonance effect (gold nanoparticles). In this chapter we describe recent developments with inorganic NPs in the PDT domain. Pertinent examples selected from the literature are used to illustrate advances in the field. We do not consider either polymeric nanoparticles or quantum dots, as these are developed in other chapters.

Présentation Poster; International audience

International audience; The aim of this review is to provide a summary of the use of copper-catalyzed azide-alkyne cycloaddition (CuAAC) in the synthesis of porphyrin, chlorin and phthalocyanine derivatives for different types of therapeutic applications. The click reaction is a powerful and versatile tool for scientists working on the synthesis of various symmetrically and asymmetrically substituted tetrapyrrolic derivatives. For example, click chemistry is widely used for the elaboration of photosensitizer conjugates for photodynamic therapy applications. Other biological applications are also described.

An improved procedures for the synthesis of 5'-O-allylthymidine via one step selective allylation of thymidine using either ultrasound or microwave activation is described.

Metal-free one-pot oxidative amidation of aldoses with functionalized amines using iodine provides a rapid access to functionalized aldonamides. The main advantage of this approach relies on the fact that aldehyde oxidation and C-N bond formation are performed in a single synthetic operation.

Metal-free one-pot oxidative amidation of aldoses with functionalized amines using iodine provides a rapid access to functionalized aldonamides. The main advantage of this approach relies on the fact that aldehyde oxidation and C-N bond formation are performed in a single synthetic operation.