N-Heterocyclic Carbene-Platinum Complexes Featuring an Anthracenyl Moiety: Anti-Cancer Activity and DNA Interaction

A platinum (II) complex stabilized by a pyridine and an N-heterocyclic carbene ligand featuring an anthracenyl moiety was prepared. The compound was fully characterized and its molecular structure was determined by single-crystal X-ray diffraction. The compound demonstrated high in vitro antiproliferative activities against cancer cell lines with IC50 ranging from 10 to 80 nM. The presence of the anthracenyl moiety on the N-heterocyclic carbene (NHC) Pt complex was used as a luminescent tag to probe the metal interaction with the nucleobases of the DNA through a pyridine-nucleobase ligand exchange. Such interaction of the platinum complex with DNA was corroborated by optical tweezers techniques and liquid phase atomic force microscopy (AFM). The results revealed a two-state interaction between the platinum complex and the DNA strands. This two-state behavior was quantified from the different experiments due to contour length variations. At 24 h incubation, the stretching curves revealed multiple structural breakages, and AFM imaging revealed a highly compact and dense structure of platinum complexes bridging the DNA strands

Etude des structures secondaires de molécules uniques d'ARN post et en cours de transcription

Dans les années 80, de nombreuses études sur certains ARN ont montré qu'ils possédaient des propriétés biologiques qui jusqu'alors n'étaient attribuées aux seules protéines. Dès lors de nombreux ARN de ce type ont été découvert et la corrélation entre la structure tertiaire et les propriétés biologiques est très forte. Dans ce travail nous avons développé de nouveaux outils permettant de définir les structures de ces ARN. La première technique est une dénaturation mécanique par les pinces optiques : la signature de cette dénaturation est directement lié aux structures en présence. La deuxième technique est de suivre le repliement et donc la structure des ARN en cours de transcription par microscopie en onde évanescente. Ces deux techniques ont été complétées par des simulations numériques.In the 80th, people working on RNA discovered that some of them had some biological properties. This properties were at that time only attributed to proteins. Since that many other RNA with properties has been discovered, and the correlation between function and structure has been shown. In that work we built some new techniques to define the structures. The first tool built was based on mechanical denaturation. This denaturation were obtained by optical tweezers, the signature of such denaturation is directly related to structure. The second setup build was to follow the folding during transcription by using evanescent wave microscopy. This two techniques were completed by some numerical simulations.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Toward Clinical Transfer of Tumor‐Targeted Ultrasmall Inorganic Nanoparticles

International audienceUltrasmall nanoparticles (USNs) (nanoparticles with hydrodynamic diameter <10 nm) are being widely developed pre-clinically and started to emerge in clinical trials over the last decade. Most of these USNs display the same features including short retention time in the blood, rapid renal clearance, and relie on passive targeting strategy to reach the tumor. Through this review, the development of AGuIX USNs is focused on because of their clinical usages as passively targeted USN but also because of their possible biofunctionalizations with peptides and monoclonal antibodies which are validated in various pre-clinical tumor models. As a result, the authors reviewed all the current biofunctionalization strategies that can be employed and confirmed based on a meta-analysis of the literature that biofunctionalized USNs pharmacokinetic and biodistribution profiles are dictated by the USNs and not the active targeting moiety. Additionally, it is demonstrated that such active targeting strategy improves the tumor targeting efficiency of the AGuIX USN but also increases their tumor retention time in comparison to the passively targeted AGuIX USNs, which may lead to an opportunity to reduce the number of injections/expend the therapeutic benefit of the drug product

Influence de la mécanique des fluides sur la formation des métastases (Influence of fluid mechanics on metastasis formation)

Metastases are the main cause of cancer-related deaths. The chain of events leading to their development is called "the metastatic cascade". The biological and biochemical aspects of this process have been well studied but the importance of biomechanical parameters only recently became a focus in the field. Studies have shown the biological fluids (blood, lymph and interstitial fluid) to play a key role in the metastatic cascade. These fluids participate in the transport of circulating tumor cells (CTCs) as well as the factors that they secrete, while at the same time influencing the events of the metastatic cascade through the forces that they generate. The hemodynamic properties and topological constraints of the vascular architecture control the formation of metastatic niches and the metastatic potential of tumor cells. In this review, we discuss the importance of these mechanical forces and highlight the novel questions and research avenues that they open

Melt-Processed Anhydrous Proton Exchange Membranes for Fuel Cell Applications

Peer reviewed: NoNRC publication: Ye

Core-shell iron oxide@stellate mesoporous silica for combined nearinfrared photothermia and drug delivery : influence of pH and surface chemistry

International audienceThe chemical design of smart nanocarriers, providing in one nanoformulation combined anticancer therapies, still remains a challenge in the field of nanomedicine. Among nanomaterials, iron oxide-based coreshell nanostructures have been already studied for their intrinsic magnetic hyperthermia features that may be coupled with drug delivery. However, despite the great interest today for photo-induced hyperthermia, very few studies investigated the potential of such nanocarriers to combine photothermia and drug delivery. In this work, our aim was to design functional iron oxide@stellate mesoporous silica nanoparticles (denoted IO@STMS NPs) loaded with a drug and able to combine in a same formulation near infrared (NIR) light induced photothermia with antitumor drug release. Herein, the NIR photothermal properties (SAR, specific absorption rates) of such nanomaterials were quantified for the first time as a function of the laser power and the NP amount. Aside the response to NIR light, the conditions to obtain very high drug loading (drug payloads up to 91 wt%) of the model antitumor drug doxorubicin (DOX) were optimized by varying different parameters, such as the NP surface chemistry (BARE (Si-OH), aminopropylsiloxane (APTES) and isobutyramide (IBAM)) and the pH of the drug impregnation aqueous solution. The drug release study of these core-shell systems in the presence or absence of NIR light demonstrated that the DOX release efficiency is mainly influenced by two parameters: surface chemistry (BARE ≥ IBAM ≥ APTES) and pH (pH 5.5 ≥ pH 6.5 ≥ pH 7.5). Furthermore, the temperature profiles under NIR light are found similar and independent from the pH range, the surface chemistry and the cycle number. Hence, the combination of local photothermia with lysosomal-like pH induced drug delivery (up to 40% release of the loaded drug) with these nanostructures could open the way towards new drug delivery nanoplatforms for nanomedecine applications

Subcellular Localization and Transport Kinetics of Ruthenium Organometallic Anticancer Compounds in Living Cells: A Dose-Dependent Role for Amino Acid and Iron Transporters:

Ruthenium-based compounds are developed for anticancer treatment, but their mode of action including their import mechanism and subcellular localization remains elusive. Here, we used the intrinsic luminescent properties of cytotoxic organoruthenium (Ru(II)) compounds obtained with an anionic cyclometalated 2-phenylpyridine chelate and neutral aromatic chelating ligands (e.g., phenanthrolines) to follow their behavior in living cells. We established that the difference in sensitivity between cancer cells and noncancerous cells toward one of the compounds correlates with its import kinetics and follows a balance between active and passive transport. The active-transport mechanism involves iron and amino-acid transporters, which are transcriptionally regulated by the drug. We also demonstrated a correlation between the accumulation of these compounds in specific compartments (endoplasmic reticulum, nucleus, mitochondria) and the activation of specific cytotoxic mechanisms such as the rnitochondrial stress pathway. Our study pinpoints a novel and complex mechanism of accumulation of ruthenium drugs in cancer cells