45 research outputs found
Mise en évidence du potentiel biomédical de nouveaux nanovecteurs
No full textThe development of targeted therapies is a major health issue and the rise of nanovectors makes it possible to meet these clinical needs. The first approach of this thesis is dedicated to the study of the therapeutic potential of multifunctional nanoparticles for medical imaging, photothermal therapy and drug delivery in cancer treatment. The second line of research focuses on active therapeutic targeting. The NanoMedSyn company aims to develop an active targeting of the mannose 6-phosphate receptor, allowing a better addressing of drugs and more effective treatments. This type of targeting may have multiple benefits for cancer therapy but also for the treatment of the lysosomal diseases which are rare genetic diseases. NanoMedSyn develops innovative synthetic derivatives of glycovectors, called AMFA, which it exploits exclusively. AMFA have a good affinity for the mannose 6-phosphate receptor and have been grafted on multifunctional nanoparticles in order to improve addressing and two-photon photodynamic therapy of a pediatric cancer: the rhabdomyosarcoma; and on lysosomal enzymes for the lysosomal diseases treatment such as for Pompe disease.Le développement de thérapies ciblées est un enjeu majeur en santé et l’essor des nanovecteurs permet de répondre à ces besoins cliniques. Le premier axe de cette thèse est consacré à l’étude du potentiel thérapeutique de nanoparticules multifonctionnelles pour l’imagerie médicale, la thérapie photothermique et la délivrance de drogue pour le traitement du cancer. Le deuxième axe de recherche s’oriente vers le ciblage thérapeutique actif. L’entreprise NanoMedSyn a pour objectif de développer un ciblage actif du récepteur du mannose 6-phosphate, permettant un meilleur adressage des médicaments et des traitements plus efficaces. Ce type de ciblage peut avoir des retombées multiples pour la thérapie anticancéreuse mais également pour la thérapie des maladies lysosomales qui sont des maladies génétiques rares. NanoMedSyn développe des dérivés synthétiques de glycovecteurs innovants, appelés AMFA, qu’elle exploite en exclusivité. Les AMFA ont une bonne affinité pour le récepteur du mannose 6-phosphate et ont été greffés sur des nanoparticules multifonctionnelles dans le but d’améliorer l’adressage et la thérapie photodynamique biphotonique d’un cancer pédiatrique : le rhabdomyosarcome ; et sur des enzymes lysosomales pour le traitement de maladies lysosomales telle que la maladie de Pompe
New nanocarriers therapeutic potential investigation
No full textLe développement de thérapies ciblées est un enjeu majeur en santé et l’essor des nanovecteurs permet de répondre à ces besoins cliniques. Le premier axe de cette thèse est consacré à l’étude du potentiel thérapeutique de nanoparticules multifonctionnelles pour l’imagerie médicale, la thérapie photothermique et la délivrance de drogue pour le traitement du cancer. Le deuxième axe de recherche s’oriente vers le ciblage thérapeutique actif. L’entreprise NanoMedSyn a pour objectif de développer un ciblage actif du récepteur du mannose 6-phosphate, permettant un meilleur adressage des médicaments et des traitements plus efficaces. Ce type de ciblage peut avoir des retombées multiples pour la thérapie anticancéreuse mais également pour la thérapie des maladies lysosomales qui sont des maladies génétiques rares. NanoMedSyn développe des dérivés synthétiques de glycovecteurs innovants, appelés AMFA, qu’elle exploite en exclusivité. Les AMFA ont une bonne affinité pour le récepteur du mannose 6-phosphate et ont été greffés sur des nanoparticules multifonctionnelles dans le but d’améliorer l’adressage et la thérapie photodynamique biphotonique d’un cancer pédiatrique : le rhabdomyosarcome ; et sur des enzymes lysosomales pour le traitement de maladies lysosomales telle que la maladie de Pompe.The development of targeted therapies is a major health issue and the rise of nanovectors makes it possible to meet these clinical needs. The first approach of this thesis is dedicated to the study of the therapeutic potential of multifunctional nanoparticles for medical imaging, photothermal therapy and drug delivery in cancer treatment. The second line of research focuses on active therapeutic targeting. The NanoMedSyn company aims to develop an active targeting of the mannose 6-phosphate receptor, allowing a better addressing of drugs and more effective treatments. This type of targeting may have multiple benefits for cancer therapy but also for the treatment of the lysosomal diseases which are rare genetic diseases. NanoMedSyn develops innovative synthetic derivatives of glycovectors, called AMFA, which it exploits exclusively. AMFA have a good affinity for the mannose 6-phosphate receptor and have been grafted on multifunctional nanoparticles in order to improve addressing and two-photon photodynamic therapy of a pediatric cancer: the rhabdomyosarcoma; and on lysosomal enzymes for the lysosomal diseases treatment such as for Pompe disease
Biological Assessment of Laser-Synthesized Silicon Nanoparticles Effect in Two-Photon Photodynamic Therapy on Breast Cancer MCF-7 Cells
No full textInternational audienceDriven by their distinctive physiological activities, biological properties and unique theranostic modalities, silicon nanoparticles (SiNPs) are one of the promising materials for the development of novel multifunctional nanoplatforms for biomedical applications. In this work, we assessed the possibility to use laser-synthesized Si NPs as photosensitizers in two-photon excited photodynamic therapy (TPE-PDT) modality. Herein, we used an easy strategy to synthesize ultraclean and monodispersed SiNPs using laser ablation and fragmentation sequences of silicon wafer in aqueous solution, which prevent any specific purification step. Structural analysis revealed the spherical shape of the nanoparticles with a narrow size distribution centered at the mean size diameter of 62 nm ± 0.42 nm, while the negative surface charge of −40 ± 0.3 mV ensured a great stability without sedimentation over a long period of time. In vitro studies on human cancer cell lines (breast and liver) and healthy cells revealed their low cytotoxicity without any light stimulus and their therapeutic potential under TPE-PDT mode at 900 nm with a promising cell death of 45% in case of MCF-7 breast cancer cells, as a consequence of intracellular reactive oxygen species release. Their luminescence emission inside the cells was clearly observed at UV-Vis region. Compared to Si nanoparticles synthesized via chemical routes, which are often linked to additional modules with photochemical and photobiological properties to boost photodynamic effect, laser-synthesized SiNPs exhibit promising intrinsic therapeutic and imaging properties to develop advanced strategy in nanomedicine field
The mannose 6-phosphate receptor targeted with porphyrin-based periodic mesoporous organosilica nanoparticles for rhabdomyosarcoma theranostics
No full textInternational audiencePorphyrin-based periodic mesoporous organosilica nanoparticles (PMO) synthesized from a large functional octatriethoxysilylated porphyrin precursor and allowing two-photon excitation photodynamic therapy (TPE-PDT) and NIR imaging were synthesized. These PMO were grafted with polyethylene glycol (PEG) moieties and an analogue of mannose 6-phosphate functionalized at the anomeric position (AMFA). AMFAs are known to efficiently target mannose 6-phosphate receptors (M6PRs) which are over-expressed in various cancers. Here, we demonstrated for the first time that M6PRs were over-expressed in rhabdomyosarcoma (RMS) cells and could be efficiently targeted with PMO–AMFA allowing TPE imaging and TPE-PDT of RMS cells. The comparison with healthy myoblasts demonstrated an absence of biological effects, suggesting a cancer cell specificity in the biomedical action observe
In vitro toxicity and photodynamic properties of porphyrinoids bearing imidazolium salts and N-heterocyclic carbene gold(I) complexes
No full textPorphyrins bearing imidazolium salts were synthesized and used as N-heterocylic carbene (NHC) precursors for the preparation of gold(I) complexes. The dark toxicity and phototoxicity of the obtained compounds were investigated in vitro on MCF-7 breast cancer cells. The obtained data showed that porphyrins equipped with imidazolium salts are non-toxic in the dark and present interesting photodynamic properties. On the contrary, corresponding NHC-gold(I) complexes are not suitable photosensitizers for photodynamic therapy (PDT) applications. Their dark toxicity strongly depends on the nature of the linker between the porphyrin core and the NHC. This work was extended to the synthesis of a pyropheophorbide a derivative with a pendant imidazolium group for PDT applications using excitation wavelengths of 450 nm, 545 nm, and importantly of 650 nm
<i>In vitro</i> toxicity and photodynamic properties of porphyrinoids bearing imidazolium salts and N-heterocyclic carbene gold(I) complexes
No full textLarge Pore Mesoporous Silica and Organosilica Nanoparticles for Pepstatin A Delivery in Breast Cancer Cells
No full text(1) Background: Nanomedicine has recently emerged as a new area of research, particularly to fight cancer. In this field, we were interested in the vectorization of pepstatin A, a peptide which does not cross cell membranes, but which is a potent inhibitor of cathepsin D, an aspartic protease particularly overexpressed in breast cancer. (2) Methods: We studied two kinds of nanoparticles. For pepstatin A delivery, mesoporous silica nanoparticles with large pores (LPMSNs) and hollow organosilica nanoparticles (HOSNPs) obtained through the sol–gel procedure were used. The nanoparticles were loaded with pepstatin A, and then the nanoparticles were incubated with cancer cells. (3) Results: LPMSNs were monodisperse with 100 nm diameter. HOSNPs were more polydisperse with diameters below 100 nm. Good loading capacities were obtained for both types of nanoparticles. The nanoparticles were endocytosed in cancer cells, and HOSNPs led to the best results for cancer cell killing. (4) Conclusions: Mesoporous silica-based nanoparticles with large pores or cavities are promising for nanomedicine applications with peptides
Development of targeted photodynamic therapy drugs by combining a zinc phthalocyanine sensitizer with TSPO or EGFR binding groups: the impact of the number of targeting agents on biological activity
No full textInternational audienceDrug-targeted delivery has become a top priority in the world of medicine in order to develop more efficient therapeutic agents. This is important as a critical underlying problem in cancer therapy stems from the inability to deliver active therapeutic substances directly to tumor cells without causing collateral damage. In this work, zinc(II) phthalocyanine (ZnPc) was selected as a sensitizer and was linked to different targeting agents, which would be recognized by overexpressed proteins in cancer cells. As targeting agents, we first selected the two ligands (DAA1106, PK11195) of the translocator protein (TSPO) and then Erlotinib a binding group of the ATP domain of tyrosine kinase in epidermal growth factor (EGFR). ZnPc was connected via an ethylene glycol chain to either one (n = 1) or four (n = 4) targeting agents. The biological activity of these conjugates ZnPc(ligand)n was investigated on MDA-MB-231 breast human cancer cells and human hepatoma HepG2 cells, first in the dark (cytotoxicity) and then under irradiation (photodynamic therapy). The dark cytotoxicity was extremely low (IC50 ≥ 50 μM) for all of these compounds, which is a required criterion for further photodynamic application. After irradiation at 650 nm, only the conjugates bearing one targeting ligand such as ZnPc-[DAA1106]1, ZnPc-[PK11195]1, and ZnPc-[Erlo]1 showed photodynamic activity, while those linked to 4 targeting agents were inactive. Importantly, fluorescence imaging microscopy showed the colocalization of ZnPc-[DAA1106]1, ZnPc-[PK11195]1 and ZnPc-[erlo]1, at mitochondria, a result that justifies the observed photodynamic activity of these conjugates. This study first shows the impact of the number and the mode of organization of targeting agents on the ability of the sensitizer to cross the cell membrane. When zinc(II) phthalocyanine carries a single targeting agent, a significant photodynamic activity on MDA-MB-231 breast human cancer cells was measured and localization at the mitochondria was demonstrated by fluorescence imaging, thus proving the potential of the sensitizer linked to a targeting agent to improve selectivity. Another important conclusion from this study for the design of future effective PDT drugs using multivalence effects is to control the arrangement of the targeting agents in order to design molecules that will be able to pass the cell membrane barriers
Potential application of oxidized cellulose/alginate loaded hydroxyapatite/graphene oxide beads in bone tissue engineering
No full textAbstract Bone regeneration is one of the most effective methods for treating bone defects. In this work, tricarboxylic cellulose/sodium alginate loaded with hydroxyapatite (HA) and/or graphene oxide (GO) was coagulated by calcium ions to create beads as scaffolds. In the first, cellulose was oxidized to water-soluble tricarboxylic cellulose (TCC) by 2,2,6,6‐tetramethylpiperidine-1-oxyl (TEMPO), periodate, and chlorite oxidation. HA was extracted from eggshells via microwave treatment, and GO was synthesized using the Hummer method. The structural behavior of the formed beads was meticulously investigated through various characterization techniques such as Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The SEM images confirmed the formation of particles of micrometric size without any specific morphology. Incorporating GO or HA does not affect the morphologies of the materials on the micrometric scale. The cytocompatibility of different bead preparations was studied on murine mesenchymal stem cells. Moreover, the swellability in water and biodegradability by cellulase enzyme of prepared beads were studied. The results show that the prepared beads may be promising for bone tissue engineering
A High Performace of Local Binary Pattern on Classify Javanese Character Classification
No full textThe classification of Javanese character images is done with the aim of recognizing each character. The selected classification algorithm is K-Nearest Neighbor (KNN) at K = 1, 3, 5, 7, and 9. To improve KNN performance in Javanese character written by the author, and to prove that feature extraction is needed in the process image classification of Javanese character. In this study selected Local Binary Patter (LBP) as a feature extraction because there are research objects with a certain level of slope. The LBP parameters are used between [16 16], [32 32], [64 64], [128 128], and [256 256]. Experiments were performed on 80 training drawings and 40 test images. KNN values after combination with LBP characteristic extraction were 82.5% at K = 3 and LBP parameters [64 64]
