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

International audienceA 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

Seeing is believing - multi-scale spatio-temporal imaging towards in vivo cell biology

Life is driven by a set of biological events that are naturally dynamic and tightly orchestrated from the single molecule to entire organisms. Although biochemistry and molecular biology have been essential in deciphering signaling at a cellular and organismal level, biological imaging has been instrumental for unraveling life processes across multiple scales. Imaging methods have considerably improved over the past decades and now allow to grasp the inner workings of proteins, organelles, cells, organs and whole organisms. Not only do they allow us to visualize these events in their most-relevant context but also to accurately quantify underlying biomechanical features and, so, provide essential information for their understanding. In this Commentary, we review a palette of imaging (and biophysical) methods that are available to the scientific community for elucidating a wide array of biological events. We cover the most-recent developments in intravital imaging, light-sheet microscopy, super-resolution imaging, and correlative light and electron microscopy. In addition, we illustrate how these technologies have led to important insights in cell biology, from the molecular to the whole-organism resolution. Altogether, this review offers a snapshot of the current and state-of-the-art imaging methods that will contribute to the understanding of life and disease

Design of Protein‐Coated Carbon Nanotubes Loaded with Hydrophobic Drugs through Sacrificial Templating of Mesoporous Silica Shells

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Nanocomposite Polymer Scaffolds Responding under External Stimuli for Drug Delivery and Tissue Engineering Applications

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Wrapped stellate silica nanocomposites as biocompatible luminescent nanoplatforms assessed in vivo

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Fluids and their mechanics in tumour transit: shaping metastasis

International audienceThe Greek phrase 'Panta Rhei' , which literally translates as 'everything flows' , is a philosophical concept that is often attributed to the presocratic Greek philosopher Heraclitus (circa 500 bc) and was an attempt to explain the ever-changing nature of life. Work over the past decades has shown that this notion might also apply to tumour metastasis, a complex multistep process whereby malignant tumours shed invasive cells with metastatic capacity that need to overcome many obstacles (for example, immune surveillance) for successful outgrowth at secondary sites 1. However, in addition to the multiple molecular pathways driving metastasis, a plethora of studies conducted over the past two decades strongly suggest that mechanical forces are also responsible for tumour progression and response to classical therapies 2-4. Among these forces, fluid-based mechanics have progressively entered the scene. Indeed, on their way to forming a metastasis, tumour cells and tumour-secreted factors use and exploit three main bodily fluids-blood, lymph and interstitial fluid 5-7 (Fig. 1a). Circulating tumour cells (CTCs) and their associated material, including soluble factors and extracellular vesicles (EVs), can directly travel through the haematogenous system 1,8 or sequentially use both the lymphatic and blood vasculature to colonize distant organs 9-11 (Fig. 1b). This notion that fluid-based mechanics can shape metastasis originated from an early pivotal study that coined the 'hemodynamic theory' , which showed that arterial blood flow in certain organs can be positively correlated with the frequency and patterns of metasta-sis 12 , supporting a link between flow mechanics and the secondary site of metastasis. When transported in fluids, CTCs are subjected to and exploit various mechanical forces, which can influence their fate in many ways. For instance, high shear forces exerted on CTCs can induce mechanical stress, leading to cell fragmentation and death 13 , whereas intermediate shear forces have been shown to favour CTC intravascular arrest and extravasation 14. Thus, an improved understanding of the mechanical forces encountered by CTCs and tumour-associated material in fluids is crucial for fully elucidating the metastatic cascade and delineating vulnerable CTC states for therapeutic intervention. In this Review, we describe how circulating tumour-derived material (cells and associated factors) use bodily fluids, their underlying forces and the resultant stresses they impose as a natural means to escape from primary tumours, travel throughout the body, prime pre-metastatic niches (PMNs) and successfully seed distant metastases. We briefly discuss key flow-related aspects of tumour growth and invasion that have received considerable attention 2,6,7 and discuss how these modes of flow are essential means of transport Fluids and their mechanics in tumour transit: shaping metastasis Abstract | Metastasis is a dynamic succession of events involving the dissemination of tumour cells to distant sites within the body , ultimately reducing the survival of patients with cancer. To colonize distant organs and, therefore, systemically disseminate within the organism, cancer cells and associated factors exploit several bodily fluid systems, which provide a natural transportation route. Indeed, the flow mechanics of the blood and lymphatic circulatory systems can be co-opted to improve the efficiency of cancer cell transit from the primary tumour, extravasation and metastatic seeding. Flow rates, vessel size and shear stress can all influence the survival of cancer cells in the circulation and control organotropic seeding patterns. Thus, in addition to using these fluids as a means to travel throughout the body , cancer cells exploit the underlying physical forces within these fluids to successfully seed distant metastases. In this Review , we describe how circulating tumour cells and tumour-associated factors leverage bodily fluids, their underlying forces and imposed stresses during metastasis. As the contribution of bodily fluids and their mechanics raises interesting questions about the biology of the metastatic cascade, an improved understanding of this process might provide a new avenue for targeting cancer cells in transit

Engineering of Mesoporous Silica Coated Carbon-Based Materials Optimized for an Ultrahigh Doxorubicin Payload and a Drug Release Activated by pH, T , and NIR-light

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3D single cell migration driven by temporal correlation between oscillating force dipoles

International audienceDirectional cell locomotion requires symmetry breaking between the front and rear of the cell. In some cells, symmetry breaking manifests itself in a directional flow of actin from the front to the rear of the cell. Many cells, especially in physiological 3D matrices, do not show such coherent actin dynamics and present seemingly competing protrusion/retraction dynamics at their front and back. How symmetry breaking manifests itself for such cells is therefore elusive. We take inspiration from the scallop theorem proposed by Purcell for micro-swimmers in Newtonian fluids: self-propelled objects undergoing persistent motion at low Reynolds number must follow a cycle of shape changes that breaks temporal symmetry. We report similar observations for cells crawling in 3D. We quantified cell motion using a combination of 3D live cell imaging, visualization of the matrix displacement, and a minimal model with multipolar expansion. We show that our cells embedded in a 3D matrix form myosin-driven force dipoles at both sides of the nucleus, that locally and periodically pinch the matrix. The existence of a phase shift between the two dipoles is required for directed cell motion which manifests itself as cycles with finite area in the dipole-quadrupole diagram, a formal equivalence to the Purcell cycle. We confirm this mechanism by triggering local dipolar contractions with a laser. This leads to directed motion. Our study reveals that these cells control their motility by synchronizing dipolar forces distributed at front and back. This result opens new strategies to externally control cell motion as well as for the design of micro-crawlers

A Ruthenium-Containing Organometallic Compound Reduces Tumor Growth through Induction of the Endoplasmic Reticulum Stress Gene CHOP

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Pulse propagation by a capacitive mechanism drives embryonic blood flow

Pulsatile flow is a universal feature of the blood circulatory system in vertebrates and can lead to diseases when abnormal. In the embryo, blood flow forces stimulate vessel remodeling and stem cell proliferation. At these early stages, when vessels lack muscle cells, the heart is valveless and the Reynolds number (Re) is low, few details are available regarding the mechanisms controlling pulses propagation in the developing vascular network. Making use of the recent advances in optical-tweezing flow probing approaches, fast imaging and elastic-network viscous flow modeling, we investigated the blood-flow mechanics in the zebrafish main artery and show how it modifies the heart pumping input to the network. The movement of blood cells in the embryonic artery suggests that elasticity of the network is an essential factor mediating the flow. Based on these observations, we propose a model for embryonic blood flow where arteries act like a capacitor in a way that reduces heart effort. These results demonstrate that biomechanics is key in controlling early flow propagation and argue that intravascular elasticity has a role in determining embryonic vascular function