Papers by Philippe Barthélémy
Scientific Reports, Jun 22, 2015
Pharmaceutics
The Autophagy Lysosomal Pathway is one of the most important mechanisms for removing dysfunctiona... more The Autophagy Lysosomal Pathway is one of the most important mechanisms for removing dysfunctional cellular components. Increasing evidence suggests that alterations in this pathway play a pathogenic role in Parkinson’s disease, making it a point of particular vulnerability. Numerous studies have proposed nanotechnologies as a promising approach for delivering active substances within the central nervous system to treat and diagnose neurodegenerative diseases. In this context, the aim was to propose the development of a new pharmaceutical technology for the treatment of neurodegenerative diseases. We designed a trehalose-based nanosystem by combining both a small natural autophagy enhancer molecule named trehalose and an amphiphilic nucleolipid conjugate. To improve nucleolipid protection and cellular uptake, these conjugates were formulated by rapid mixing in either solid lipid nanoparticles (Ø = 120.4 ± 1.4 nm) or incorporated into poly(lactic-co-glycolic acid) nanoparticles (Ø = ...
Soft Matter
β-Galactosidase instructed supramolecular assemblies of Low Molecular Weight Gelators (LMWGs) der... more β-Galactosidase instructed supramolecular assemblies of Low Molecular Weight Gelators (LMWGs) derived from glyconucleo-bolaamphiphiles have been designed.
Pharmaceutics, 2022
Antibiotic resistance has become a major issue in the global healthcare system, notably in the ca... more Antibiotic resistance has become a major issue in the global healthcare system, notably in the case of Gram-negative bacteria. Recent advances in technology with oligonucleotides have an enormous potential for tackling this problem, providing their efficient intrabacterial delivery. The current work aimed to apply this strategy by using a novel nanoformulation consisting of DOTAU, a nucleolipid carrier, in an attempt to simultaneously deliver antibiotic and anti-resistance oligonucleotides. Ceftriaxone, a third-generation cephalosporin, was formulated with DOTAU to form an ion pair, and was then nanoprecipitated. The obtained solid nanocapsules were characterized using FT-IR, XRD, HPLC, TEM and DLS techniques and further functionalized by the anti-resistance ONα sequence. To obtain an optimal anti-resistance activity and encapsulation yield, both the formulation protocol and the concentration of ONα were optimized. As a result, monodispersed negatively charged nanoparticles of CFX–D...
Pharmaceutics, 2021
Heat shock protein 27 (Hsp27) has an established role in tumor progression and chemo-resistance o... more Heat shock protein 27 (Hsp27) has an established role in tumor progression and chemo-resistance of castration-resistant prostate cancer (CRPC). Hsp27 protects eukaryotic translation initiation factor 4E (eIF4E) from degradation, thereby maintaining survival during treatment. Phenazine derivative compound #14 was demonstrated to specifically disrupt Hsp27/eIF4E interaction and significantly delay castration-resistant tumor progression in prostate cancer xenografts. In the present work, various strategies of encapsulation of phenazine #14 with either DOTAU (N-[5′-(2′,3′-dioleoyl)uridine]-N′,N′,N′-trimethylammonium tosylate) and DOU-PEG2000 (5′-PEG2000-2′,3′-dioleoyluridine) nucleolipids (NLs) were developed in order to improve its solubilization, biological activity, and bioavailability. We observed that NLs-encapsulated phenazine #14-driven Hsp27-eIF4E interaction disruption increased cytotoxic effects on castration-resistant prostate cancer cell line and inhibited tumor growth in ca...
RSC Advances, 2020
The first bio-inspired N-Heterocyclic Carbene (NHC)-catalyzed Stetter reaction in aqueous medium ... more The first bio-inspired N-Heterocyclic Carbene (NHC)-catalyzed Stetter reaction in aqueous medium is reported with benzaldehyde and chalcone as model substrates.
Organic & Biomolecular Chemistry, 2018
An NHC-catalyzed Stetter reaction as a conjugation step to provide nucleic acid-based bioconjugates.
In the first part of this paper a thorough analysis was made of the matrix equation C = ABA^B' 1 ... more In the first part of this paper a thorough analysis was made of the matrix equation C = ABA^B' 1 when C, A, B are normal matrices. Not included, however, was the discussion of this equation when A and B are real skew-symmetric matrices. In the present paper we complete the investigation by giving this discussion. Throughout this paper we adopt the notation and terminology of part I. We also continue the convention that all matrices appearing in this paper, except the zero matrix, are to be nonsingular. We always let J£i, K 2 denote real skew symmetric matrices. LEMMA 1. Let M be a matrix with linear elementary divisors, and let M = K X K 2 be a product of two real skew-symmetric matrices K 19 K 2. Then each eigenvalue of M has even multiplicity.
Scientific Reports, 2020
One of the greatest challenges in the field of biofabrication remains the discovery of suitable b... more One of the greatest challenges in the field of biofabrication remains the discovery of suitable bioinks that satisfy physicochemical and biological requirements. Despite recent advances in tissue engineering and biofabrication, progress has been limited to the development of technologies using polymer-based materials. Here, we show that a nucleotide lipid-based hydrogel resulting from the self-assembly of nucleotide lipids can be used as a bioink for soft tissue reconstruction using injection or extrusion-based systems. To the best of our knowledge, the use of a low molecular weight hydrogel as an alternative to polymeric bioinks is a novel concept in biofabrication and 3D bioprinting. Rheological studies revealed that nucleotide lipid-based hydrogels exhibit suitable mechanical properties for biofabrication and 3D bioprinting, including i) fast gelation kinetics in a cell culture medium and ii) shear moduli and thixotropy compatible with extruded oral cell survival (human gingival ...
Nanoscale Research Letters, 2018
Although the application of sorafenib, a small inhibitor of tyrosine protein kinases, to cancer t... more Although the application of sorafenib, a small inhibitor of tyrosine protein kinases, to cancer treatments remains a worldwide option in chemotherapy, novel strategies are needed to address the low water solubility (< 5 μM), toxicity, and side effects issues of this drug. In this context, the use of nanocarriers is currently investigated in order to overcome these drawbacks. In this contribution, we report a new type of sorafenib-based nanoparticles stabilized by hybrid nucleoside-lipids. The solid lipid nanoparticles (SLNs) showed negative or positive zeta potential values depending on the nucleoside-lipid charge. Transmission electron microscopy of sorafenib-loaded SLNs revealed parallelepiped nanoparticles of about 200 nm. Biological studies achieved on four different cell lines, including liver and breast cancers, revealed enhanced anticancer activities of Sorafenib-based SLNs compared to the free drug. Importantly, contrast phase microscopy images recorded after incubation of cancer cells in the presence of SLNs at high concentration in sorafenib (> 80 μM) revealed a total cancer cell death in all cases. These results highlight the potential of nucleoside-lipid-based SLNs as drug delivery systems.
Bioconjugate Chemistry, 2019
Oligonucleotide-based agents have the potential to treat or cure almost any disease, and are one ... more Oligonucleotide-based agents have the potential to treat or cure almost any disease, and are one of the key therapeutic drug classes of the future. Bioconjugated oligonucleotides, a subset of this class, are emerging from basic research and being successfully translated to the clinic. In this review, we first briefly describe two approaches for inhibiting specific genes using oligonucleotides-antisense DNA (ASO) and RNA interference (RNAi)followed by a discussion on delivery to cells. We then summarize and analyze recent developments in bioconjugated oligonucleotides including those possessing GalNAc, cell penetrating peptides, αtocopherol, aptamers, antibodies, cholesterol, squalene, fatty acids, or nucleolipids. These novel conjugates provide a means to enhance tissue targeting, cell internalization, endosomal escape, target binding specificity, resistance to nucleases, and more. We next describe those bioconjugated oligonucleotides approved for patient use or in clinical trials. Finally, we summarize the state of the field, describe current limitations, and discuss future prospects. Bioconjugation chemistry is at the centerpiece of this therapeutic oligonucleotide revolution, and significant opportunities exist for development of new modification chemistries, for mechanistic studies at the chemical-biology interface, and for translating such agents to the clinic.
Advanced Materials, 2018
Hybrid synthetic amphiphilic biomolecules are emerging as promising supramolecular materials for ... more Hybrid synthetic amphiphilic biomolecules are emerging as promising supramolecular materials for biomedical and technological applications. Herein, we highlight recent progress in the field of nucleic acid-based lipids with an emphasis on their molecular design, synthesis, supramolecular properties, physico-chemical behaviors and applications in the field of health science and technology. In the first section, we focus on the design and the study of nucleolipids and then discuss the glyconucleolipids family. In the last section, we describe recent contributions on responsive materials involving nucleolipids and their use as smart drug delivery systems. The supramolecular materials generated by nucleic acid-based lipids open new challenges for biomedical applications, including in the fields of medicinal chemistry, biosensors, biomaterials for tissue engineering, drug delivery and the decontamination of nanoparticles.
Molecules, 2018
Glyconanoparticles essentially result from the (covalent or noncovalent) association of nanometer... more Glyconanoparticles essentially result from the (covalent or noncovalent) association of nanometer-scale objects with carbohydrates. Such glyconanoparticles can take many different forms and this mini review will focus only on soft materials (colloids, liposomes, gels etc.) with a special emphasis on glycolipid-derived nanomaterials and the chemistry involved for their synthesis. Also this contribution presents Low Molecular Weight Gels (LMWGs) stabilized by glycoconjugate amphiphiles. Such soft materials are likely to be of interest for different biomedical applications.
Journal of tissue engineering and regenerative medicine, Jan 6, 2017
Tissue engineering is a promising alternative to autografts, allografts or biomaterials to addres... more Tissue engineering is a promising alternative to autografts, allografts or biomaterials to address the treatment of severe and large bone lesions. Classically, tissue engineering products associate a scaffold and cells, and are implanted or injected into the lesion. These cells must be embedded in an appropriate biocompatible scaffold, which offers a favourable environment for their survival and differentiation. Here, we designed a composite hydrogel composed of collagen I, an extracellular matrix protein widely used in several therapeutic applications, which we associated with a physical hydrogel generated from a synthetic small amphiphilic molecule. This composite showed improved mechanical and biological characteristics as compared with gels obtained from each separate compound. Incorporation of the physical hydrogel prevented shrinkage of collagen and cell diffusion out of the gel, and yielded a gel with a higher elastic modulus than those of gels obtained with each component al...
Journal of controlled release : official journal of the Controlled Release Society, Jul 1, 2017
Translationally controlled tumor protein (TCTP) has been implicated in a plethora of important ce... more Translationally controlled tumor protein (TCTP) has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. Therefore, TCTP is now recognized as a potential therapeutic target in several cancers including prostate, breast and lung cancers. We previously showed that TCTP is overexpressed in castration-resistant prostate cancer (CRPC), and it has been implicated resistance to treatment. Recently, we developed TCTP antisense oligonucleotides (ASOs) to inhibit TCTP expression. However, the intracellular delivery and silencing activity of these oligonucleotides remains a challenge, and depend on the use of transfection agents and delivery systems. Here we show that lipid-modified ASO (LASOs) has improved penetration and efficiency in inhibiting TCTP expression in the absence of additional transfection agents, both in vitro and in vivo. Transfection with TCTP-LASO led to rapid and p...
Advanced materials (Deerfield Beach, Fla.), Jan 2, 2017
Hydrogels formed by the self-assembly of low-molecular-weight gelators (LMWGs) are promising scaf... more Hydrogels formed by the self-assembly of low-molecular-weight gelators (LMWGs) are promising scaffolds for drug-delivery applications. A new biocompatible hydrogel, resulting from the self-assembly of nucleotide-lipid salts can be safely injected in vivo. The resulting hydrogel provides sustained-release of protein for more than a week.
Angewandte Chemie (International ed. in English), Jan 7, 2015
Controlling the behavior of stem cells through the supramolecular architecture of the extracellul... more Controlling the behavior of stem cells through the supramolecular architecture of the extracellular matrix remains an important challenge in the culture of stem cells. Herein, we report on a new generation of low-molecular-weight gelators (LMWG) for the culture of isolated stem cells. The bola-amphiphile structures derived from nucleolipids feature unique rheological and biological properties suitable for tissue engineering applications. The bola-amphiphile-based hydrogel scaffold exhibits the following essential properties: it is nontoxic, easy to handle, injectable, and features a biocompatible rheology. The reported glycosyl-nucleoside bola-amphiphiles (GNBA) are the first examples of LMWG that allow the culture of isolated stem cells in a gel matrix. The results (TEM observations and rheology) suggest that the supramolecular organizations of the matrix play a role in the behavior of stem cells in 3D environments.
Bioconjugate Chemistry, 2013
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Papers by Philippe Barthélémy