Drug development in oncology assisted by noninvasive optical imaging.

International audienceEarly and accurate detection of tumors, like the development of targeted treatments, is a major field of research in oncology. The generation of specific vectors, capable of transporting a drug or a contrast agent to the primary tumor site as well as to the remote (micro-) metastasis would be an asset for early diagnosis and cancer therapy. Our goal was to develop new treatments based on the use of tumor-targeted delivery of large biomolecules (DNA, siRNA, peptides, or nanoparticles), able to induce apoptosis while dodging the specific mechanisms developed by tumor cells to resist this programmed cell death. Nonetheless, the insufficient effectiveness of the vectorization systems is still a crucial issue. In this context, we generated new targeting vectors for drug and biomolecules delivery and developed several optical imaging systems for the follow-up and evaluation of these vectorization systems in live mice. Based on our recent work, we present a brief overview of how noninvasive optical imaging in small animals can accelerate the development of targeted therapeutics in oncology

Современные методы анализа и оценки риска

В статье проведен анализ методов оценки риска, рассмотрена их классификация. Представлен краткий обзор современных методов анализ риска и выявлены наиболее эффективные

Polymeric Nanohybrids as a New Class of Therapeutic Biotransporters

This is the peer reviewed version of the following article: Macromol Chem Phys. 2016 Jun; 217(11): 1245–1259., which has been published in final form at http://doi.org/10.1002/macp.201500464. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.A possible solution to enhance existing drug and gene therapies is to develop hybrid nanocarriers capable of delivering therapeutic agents in a controlled and targeted manner. This goal can be achieved by designing nanohybrid systems, which combine organic or inorganic nanomaterials with biomacromolecules into a single composite. The unique combination of properties along with their facile fabrication enables the design of smart carriers for both drug and gene delivery. These hybrids can be further modified with cell targeting motifs to enhance their biological interactivity. In this Talents and Trends article, an overview of emerging nanohybrid-based technologies will be provided to highlight their potential use as innovative platforms for improved cancer therapies and new strategies in regenerative medicine. The clinical relevance of these systems will be reviewed to define the current challenges which still need to be addressed to allow these therapies to move from bench to bedside

Synthèse de nouveaux vecteurs peptidiques pour la thérapie anticancéreuse et l'imagerie tumorale

Current research on cancer focuses on “targeted strategies” in order to develop sensitive and powerful diagnostic methods, as well as effective and better tolerated therapies. In this context, our works are devoted to the design of synthetic vectors targeting a cellular receptor, the alphaVbeta3 integrin, which is over-expressed in tumours. This allows the accumulation of drugs or detection elements in tumours. The tool used for the construction of our vectors is a cyclodecapeptide scaffold (RAFT: Regioselectively Addressable Functionalized Template) which presents two independent sides and allows the separation of the vector functions. On one side, the targeting function is provided by multivalent presentation of -RGD- specific ligands for the alphaVbeta3 integrin. The other side of the vector supports the molecules of interest for the delivery of therapeutic agents to limit the proliferation of tumours or detection agents for medical imaging.La recherche actuelle sur le cancer se tourne vers des « stratégies ciblées » afin de développer de nouvelles méthodes diagnostiques plus sensibles et performantes, ainsi que de nouvelles thérapies plus efficaces mais aussi mieux tolérées. Dans ce contexte, nos travaux sont consacrés à la conception de vecteurs synthétiques ciblant un récepteur cellulaire surexprimé par les tumeurs, l'intégrine alphaVbeta3. Ce ciblage permet de concentrer les drogues ou les éléments de détection au niveau tumoral. L'outil utilisé pour la construction chimique de nos vecteurs est un châssis décapeptidique cyclique RAFT (Regioselectively Addressable Functionalized Template) présentant deux domaines indépendants permettant de séparer les deux fonctions du vecteur. Sur un domaine, la fonction de ciblage est assurée par la présentation multivalente de ligands -RGD- spécifiques du récepteur. L'autre domaine du vecteur supporte les molécules d'intérêt à vectoriser : agents thérapeutiques pour limiter la prolifération du foyer malin ou agents de détection pour l'imagerie médicale

Synthesis and Biological Characterisation of Targeted Pro-Apoptotic Peptide

We report herein the synthesis and in vitro assay of new, multimeric RGD-peptide conjugates for cell-targeted drug delivery. We generated a peptide scaffold comprising two functional domains, one a tumour blood vessel homing motif and the other a programmed cell-death-inducing peptide sequence. RGD peptides were selected to direct the molecular conjugate to V 3 integrin-containing tumour cells. The pro-apoptotic (Lys-Leu-Ala-Lys-Leu-Ala-Lys)2 peptide was found to be nontoxic outside cells, but toxic when internalized into targeted cells as it disrupted the mitochondrial membrane. The synthesis of these targeted pro-apoptotic conjugates was carried out by assembling three different units (that is, scaffold, RGD units and pro-apoptotic peptide) through chemoselective ligations. We show that one compound displays significant biological effect in V 3 integrin-containing tumour cells

Utilisation du Cellcept® dans la transplantation de cellules souches hématopoïétiques en pédiatrie

LYON1-BU Santé (693882101) / SudocSudocFranceF

Highly efficient cell adhesion on beads functionalized with clustered peptide ligands

International audienc

One-Pot Approach to Well-Defined Biomolecular Assemblies by Orthogonal Chemoselective Ligations

International audienc

Polyethylenimine-carbon nanotube nanohybrids for siRNA-mediated gene silencing at cellular level

Carbon nanotubes (CNTs) covalently modified with low molecular weight polyethylenimine (PEI) are able to bind and deliver siRNA to cells with higher efficacy than a reference lipidic carrier. The performances of the nanohybrid are rationalized by the combination of the cell penetration and endosomal escape properties of CNTs and PEI, respectively