Sebastien Harlepp

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• Dr.
• Research Associate at University of Strasbourg

The development of injectable hydrogels that respond to physiological stimuli represents a promising strategy for a range of biomedical applications, although the precise tuning of gelation kinetics, mechanical stability, and biocompatibility remains a significant challenge. This study presents a pH-and osmolarity-responsive injectable hydrogel, fo...

Orientation and steric hindrance decrease the efficiency for an antibody to attach to its specific receptor. Giving flexibility to a dendronized peptide through a small PEG fragment increases the peptides affinity to cellular receptors.

Designing iron oxide nanoparticles (IONPs) to effectively combine magnetic hyperthermia (MH) and photothermia (PTT) in one IONPs formulation presents a significant challenge to ensure a multimodal therapy allowing to adapt...

Targeting the immune system with nanoparticles (NPs) to deliver immunomodulatory molecules emerged as a solution to address intra-tumoral immunosuppression and enhance therapeutic response. While the potential of nanoimmunotherapies in reactivating immune cells has been evaluated in several preclinical studies, the impact of drug-free nanomaterials...

In recent decades, subcutaneous (SC) administration of monoclonal antibodies (mAbs) has emerged as a promising alternative to intravenous delivery in oncology, offering comparable therapeutic efficacy while addressing patient preferences. This perspective article provides an in‐depth analysis of the technological landscape surrounding SC mAb admini...

In oncology, the advent of monoclonal antibody (mAbs) therapeutics represents a major breakthrough in various cancer diseases. However, these biotherapies often necessitate iterative hospital visits for intravenous infusion that can alter patient quality of life and contribute to the chronic saturation of hospitals. Interestingly, subcutaneous form...

Metastases arise from a multi-step process during which tumor cells change their mechanics in response to microenvironmental cues. While such mechanical adaptability could influence metastatic success, how tumor cell mechanics directly impacts intravascular behavior of circulating tumor cells (CTCs) remains poorly understood. In the present study,...

Nanoparticle (NP) surface functionalization with proteins, including monoclonal antibodies (mAbs), mAb fragments, and various peptides, has emerged as a promising strategy to enhance tumor targeting specificity and immune cell interaction. However, these methods often rely on complex chemistry and suffer from batch‐dependent outcomes, primarily due...

Subcutaneous (SC) administration of monoclonal antibodies (mAbs) is a proven strategy for improving therapeutic outcomes and patient compliance. The current FDA‐/EMA‐approved enzymatic approach, utilizing recombinant human hyaluronidase (rHuPH20) to enhance mAbs SC delivery, involves degrading the extracellular matrix's hyaluronate to increase tiss...

Ultrasmall 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 t...

Functionalized iron oxide nanoparticles (IONPs) are increasingly being designed as a theranostic nanoplatform combining specific targeting, diagnosis by magnetic resonance imaging (MRI), and multimodal therapy by hyperthermia. The effect of the size and the shape of IONPs is of tremendous importance to develop theranostic nanoobjects displaying eff...

Directional 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 protrusio...

The design of smart nanocomposite supramolecular scaffolds for tissue engineering or anticancer applications, able to release drugs under external fields is currently a challenge. Such architectures require not only strong interactions between the polymer matrix and externally responsive nanomaterials, but also an efficient strategy for the loading...

The blossoming development of nanomaterials and polymer science has opened the way toward new biocompatible scaffolds responding remotely to external stimuli (magnetic field, light, electric field). Such smart scaffolds are envisioned as new implantable tissues displaying multiple therapeutic and imaging functionalities. They hold great promises to a...

The 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 core-shell nanostructures have been already studied for their intrinsic magnetic hyperthermia features that may be coupled with drug delivery. Howeve...

Cancer metastasis is a multistep process during which tumor cells leave the primary tumor mass and form distant secondary colonies that are lethal. Circulating tumor cells (CTCs) are transported by body fluids to reach distant organs, where they will extravasate and either remain dormant or form new tumor foci. Development of methods to study the b...

The most dangerous aspect of cancer lies in metastatic progression. Tumor cells will successfully form life-threatening metastases when they undergo sequential steps along a journey from the primary tumor to distant organs. From a biomechanics standpoint, growth, invasion, intravasation, circulation, arrest/adhesion, and extravasation of tumor cell...

La suite d’évènements menant à l’apparition de métastases est appelée « cascade métastatique ». L’étude récente de la composante biomécanique de cette cascade a révélé le rôle central des liquides biologiques dans la dissémination métastatique. Tout en participant au transport des cellules tumorales circulantes et des facteurs qu’elles sécrètent, c...

Among smart activable nanomaterials used for nanomedicine applications, carbon-based nanocomposites are well known to ensure phototherapy while their use for controlled drug delivery is still rarely investigated. In this work, original hybrid mesoporous silica (MS)–coated carbon nanotubes (CNTs) nanoplatforms have been designed to provide photother...

The blossoming development of nanomaterials and polymer science has opened the way toward new biocompatible scaffolds responding remotely to external stimuli (magnetic field, light, electric field). Such smart scaffolds are envisioned as new implantable tissues displaying multiple therapeutic and imaging functionalities. They hold great promises to...

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...

Cancer metastasis is a process whereby a primary tumor spreads to distant organs. We have demonstrated previously that blood flow controls the intravascular arrest of circulating tumor cells (CTCs) through stable adhesion to endothelial cells. We now aim to define the contribution of cell adhesion potential and identify adhesion receptors at play....

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 I...

The engineering of luminescent nanoplatforms for biomedical applications displaying ability for scaling-up, good colloidal stability in aqueous solutions, biocompatibility, and providing an easy detection in vivo by fluorescence methods while offering high potential of functionalities, is currently a challenge. The original strategy proposed here i...

Tumor extracellular vesicles (EVs) mediate the communication between tumor and stromal cells mostly to the benefit of tumor progression. Notably, tumor EVs travel in the bloodstream, reach distant organs, and locally modify the microenvironment. However, visualizing these events in vivo still faces major hurdles. Here, we describe an approach for t...

Among the challenges in nanomedicine, engineering nanomaterials able to combine imaging and multitherapies is hugely needed to address issues of a personalized treatment. In that context, a novel class of drug releasing and remotely activated nanocomposites based on carbon-based materials coated with mesoporous silica (MS) and loaded with an outsta...

Metastatic seeding is driven by cell-intrinsic and environmental cues, yet the contribution of biomechanics is poorly known. We aim to elucidate the impact of blood flow on the arrest and the extravasation of circulating tumor cells (CTCs) in vivo. Using the zebrafish embryo, we show that arrest of CTCs occurs in vessels with favorable flow profile...

Most cancers end up with the death of patients caused by the formation of secondary tumors, called metastases. However, how these secondary tumors appear and develop is only poorly understood. A fine understanding of the multiple steps of the metastasis cascade requires in vivo models allowing high spatiotemporal analysis of the behavior of metasta...

One key challenge in the fields of nanomedecine and tissue engineering is the design of theranostic nanoplatforms able to monitor their therapeutic effect by imaging. Among current developed nano-objects, carbon nanotubes (CNTs) were found suitable to combine imaging, photothermal therapy and to be loaded with hydrophobic drugs. However, a main pro...

Force sensing and generation at the tissular and cellular scale is central to many biological events. There is a growing interest in modern cell biology for methods enabling force measurements in vivo Optical trapping allows non-invasive probing of pico-Newton forces and thus emerged as a promising mean for assessing biomechanics in vivo Neverthele...

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 mult...

Metastasis is the end product of a multistep process where cancer cells disseminate and home themselves in distant organs. Tumor cell extravasation is a rare, inefficient and transient event in nature and makes its studies very difficult. Noteworthy, little is known about how cancer cells arrest, adhere and pass through the endothelium of capillari...

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 arom...

DNA has a strong affinity for many heterocyclic aromatic dyes, such as acridine and its derivatives. Lerman in 1961 first proposed intercalation as the source of this affinity, and this mode of DNA binding has since attracted considerable research scrutiny. DNA intercalators (molecules that intercalate between DNA base pairs) have attracted particu...

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 avai...

Hydrodynamic forces play a central role in organ morphogenesis. The role of blood flow in shaping the developing heart is well established, but the role of fluid forces generated in the pericardial cavity surrounding the heart is unknown. Mesothelial cells lining the pericardium generate the proepicardium (PE), the precursor cell population of the...

The worm-like chain model describes the mechanical properties of semi-flexible polymers by introducing a certain correlation length along the contour. This correlation length is called the persistence length. Using atomic force microscopy in solution, we performed measurements of the persistence length of DNA molecules. We found good agreement betw...

Because many anticancer drugs interact with DNA, the determination of their association constants to DNA is essential for quantifying their mechanisms of action. The interactions between a new ruthenium-derived compound [ruthenium(phenanthroline)(κ-C,N-(2-phenyl-pyridine)(NCMe)(2)]PF(6), called RDC11] and DNA are studied using different techniques....

We present a method in which we stabilize mechanically an optical tweezer setup over a period ranging up to 30 min. A feedback loop is used to correct the mechanical and thermal drifts. The position of a fixed object on the sample surface is measured with a CCD device and its fluctuations analyzed and used to maintain its position fixed with three...

Cisplatin-derived anticancer therapy has been used for three decades despite its side effects. Other types of organometallic complexes, namely, some ruthenium-derived compounds (RDC), which would display cytotoxicity through different modes of action, might represent alternative therapeutic agents. We have studied both in vitro and in vivo the biol...

RNA co-transcriptional folding has long been suspected to play an active role in helping proper native folding of ribozymes and structured regulatory motifs in mRNA untranslated regions (UTRs). Yet, the underlying mechanisms and coding requirements for efficient co-transcriptional folding remain unclear. Traditional approaches have intrinsic limita...

RNA co-transcriptional folding has long been suspected to play an active role in helping proper native folding of ribozymes and structured regulatory motifs in mRNA untranslated regions. Yet, the underlying mechanisms and coding requirements for efficient co-transcriptional folding remain unclear. Traditional approaches have intrinsic limitations t...

A primitive example of adaptation in gene expression is the balance between the rate of synthesis and degradation of cellular RNA, which allows rapid responses to environmental signals. Here, we investigate how multidrug efflux pump systems mediate the dynamics of a simple drug-inducible system in response to a steady level of inducer. Using fluore...

Characterizing the dynamics of specific RNA levels requires real-time RNA profiling in a single cell. We show that the combination of a synthetic modular genetic system with fluorescence correlation spectroscopy allows us to directly measure in real time the activity of any specific promoter in prokaryotes. Using a simple inducible gene expression...

In total internal reflection microscopy (TIRM), quantitative interpretation of results often requires a precise knowledge of the penetration depth of the evanescent wave. Standard TIRM practice is to calculate this depth from the microscope’s geometry, but this can introduce significant errors. We show how to calibrate the penetration depth of an e...

RNA secondary structures of increasing complexity are probed combining single molecule stretching experiments and stochastic unfolding/refolding simulations. We find that force-induced unfolding pathways cannot usually be interpreted by solely invoking successive openings of native helices. Indeed, typical force-extension responses of complex RNA m...

The mechanical properties of composite membranes obtained by self-assembly of actin filaments with giant fluid vesicles are studied by micromanipulation with optical tweezers. These complexes exhibit typical mechanical features of a solid shell, including a finite in-plane shear elastic modulus ( approximately 10(-6) N/m). A buckling instability is...

In living cells, cytoskeletal filaments interact with the plasma membrane to form structures that play a key role in cell shape and mechanical properties. To study the interaction between these basic components, we designed an in vitro self-assembled network of actin filaments attached to the outer surface of giant unilamellar vesicles. Optical twe...

We create tailored microstructures, consisting of complexes of lipid membranes with self-assembled biopolymer shells, to study the fundamental properties and interactions of these basic components of living cells. We measure the mechanical response of these artificial structures at the micrometer scale, using optical tweezers and single-particle tr...