Caractérisations théoriques et expérimentales d'agents de contraste ultrasonore ciblés

Depuis leur introduction, les agents de contraste ont révolutionné l'imagerie échographique. Ils sont composés de microbulles gazeuses, qui injectés par voie intraveineuse dans le sang, ils améliorent l'image échographique. Une autre application pour laquelle les caractéristiques physiques des agents de contraste sont exploitées est l'imagerie ciblée. Une approche basée sur l'utilisation de ligands intégrés à la paroi des microbulles, celles-ci adhérent aux facteurs de surfaces moléculaires surexprimés par les cellules endothéliales qui tapissent la paroi interne des vaisseaux sanguins. Pour pouvoir distinguer ces microbulles de celles qui circulent librement, elles doivent réfléchir un signal acoustique suffisamment intense. Cependant, le faible taux d'adhérence des microbulles engendre une réduction du signal acoustique. Pour résoudre ce problème, il est important de déterminer l'effet des parois sur leurs dynamiques acoustiques. Dans cette thèse, nous avons étudié l effet des parois élastiques sur le comportement dynamique des microbulles constituant les agents de contraste. Dans un premier temps, un modèle théorique représentant une paroi avec une épaisseur finie a été développé. Il a été démontré que l amplitude de l écho rétrodiffusé par une microbulle proche d une paroi avec une épaisseur finie est inférieure à celui d une microbulle se trouvant dans un fluide infini. D'autres parts, pour représenter la paroi d un vaisseau sanguin, les propriétés mécaniques de la paroi élastique ont été intégrées au modèle. Il a été observé que la fréquence de résonance d une microbulle proche d une paroi est supérieure à celle dans un fluide infini. Par la suite, nous avons étudié l effet de trois types de parois sur le comportement d une microbulle parmi lesquelles la paroi d'OptiCell communément utilisée en expérimentations ultrasonores. Les résultats ont montré que la microbulle proche de la paroi d OptiCell diffuse un écho supérieur à celui de la microbulle éloignée de la paroi, lorsque la fréquence d excitation est au-dessus de sa fréquence de résonance. Nous avons constaté aussi que les petites bulles sont plus sensibles à la proximité de la paroi. Par la suite, nous avons développé un modèle décrivant une microbulle attachée à une paroi élastique. Nous avons montré que le contact direct de la bulle avec la paroi induit une diminution de l'écho par rapport à la même bulle dans un liquide infini. Le contact direct de la bulle avec la paroi engendre une augmentation de la fréquence de résonance part rapport à une bulle sans contact direct. Enfin, une étude expérimentale a montré l'avantage de l'imagerie sous-harmonique pour différencier les microbulles attachées des microbulles libres.Since they were introducted, contrast agents have revolutionized the ultrasound imaging. They are composed of tiny gaseous microbubbles and when injected intravenously into the blood, they improve the ultrasound image. Targeted imaging is another application based on the physical characteristics of contrast agents. This approach is based on the ligands incorporation into the microbubbles shell. The microbubble attach to the molecular factors overexpressed by endothelial cells, covering the inner wall of blood vessels. To distinguish these microbubbles from those freely circulating, attached microbubble have to produce an acoustic signal that is sufficiently strong. However, the low microbubbles adhesion induces a decrease of the acoustic signal. To make it possible, it is important to determine the effect of the elastic wall on their acoustic response. This thesis aimed to study the effect of elastic walls on the ultrasonic behavior of targeted microbubbles. First, a theoretical model describing a wall with finite thickness was developed. It has been shown that the scattered echo amplitude by a microbubble near a wall with finite thickness is small in comparison to the echo from a microbubble located in an infinite fluid. Furthermore, and in order to account for the effect of blood vessel wall, the mechanical properties of the wall have been incorporated into the model. The results showed that the resonane frequency of a microbubble near the wall is higher than the resonanace of the same microbubble in an infinite medium. Subsequently, we studied the effect of three types of walls on the microbubble behavior including the wall of OptiCell chamber which is commonly used in ultrasonic experiments. We have shown that microbubbles near the OptiCell wall diffuses a higher echo than those far from the wall when the excitation frequency is above the microbubble resonance frequency. On the other side, we observed that small microbubbles to the presence of the wall. Afterward, we developed a model describing a microbubble attached to the wall. We have shown that the microbubble in direct contact with the wall induces a decrease of the echo amplitude compared to the same bubble in infinite liquid. Moreover, the direct contact of the bubble with the wall generates an increase of the resonance frequency relative to a bubble without direct contact. Finally, an experimental study has shown the advantage of the subharmonic imaging to differentiate attached microbubbles from the free ones.TOURS-Bibl.électronique (372610011) / SudocSudocFranceF

Influences of Umbilical Cord Mesenchymal Stem Cells and Their Exosomes on Tumor Cell Phenotype

[EN] Backgrounds: Umbilical cord mesenchymal stem cells (UCMSCs) are derived from umbilical cord tissue. Due to their low immunogenicity, easy availability, mature culture technology, and lack of ethical controversy, they have gradually emerged as a focal point in stem cell research. Exosomes are cell-derived vesicles with a structure consistent with the cell membrane, primarily functioning as carriers to transport substrates for intercellular communication and regulation. Presently, both stem cells and their exosomes have emerged as highly promising biopharmaceuticals widely utilized in various clinical studies, including wound healing, spinal cord injury, post-operative rehabilitation, neurological disorders, and autoimmune diseases. However, the safety of these biologics remains uncertain, with some studies suggesting the potential tumorigenicity of stem cells and their exosomes. The objective of this study was to investigate the effects of UCMSCs and their exosomes on four types of tumor cells. Methods: In this study, first of all, UCMSCs and their exosomes were isolated and characterized. Subsequently, the study was performed in cell experiments. The effects of UCMSCs and their exosomes on four types of tumor cells (blast cancer cell line, gastric cancer cell line, glioma cell line, lung cancer cell line) were observed through co-culture experiments. The observables included the effects on in vitro phenotype and in vivo growth characteristics. Changes in gene expression were analyzed using high-throughput sequencing technology to elucidate the biological functions and roles of UCMSCs and their exosomes on tumor cells. Results: UCMSCs were successfully isolated, cultured, and identified. They demonstrated the capacity for differentiation into adipocytes, osteoblasts, chondrocytes, and neuron-like cells, indicating their multi-lineage differentiation potential. The UCMSCs-exos exhibited a diameter ranging from 30 to 150 nm, with an average size of 126.62 ± 1.64 nm, and showed increased expression of Tsg101, CD9, and CD63 proteins (P 0.05). However, in LN-229 cells, ROS and MDA levels were reduced, and SOD levels were increased in the UCMSCs group compared to the UCMSCs-exos group (P 0.05). In contrast, they inhibited the expression of NF-κB and p53 proteins in LN-229, with UCMSCs-exos demonstrating a more pronounced inhibitory effect (P < 0.05). Conclusions: In conclusion, this study successfully isolated UCMSCs and their exosomes. They promote the proliferation, migration, and invasion of four types of tumor cells involves altering the cell cycle. Additionally, UCMSCs and their extracellular vesicles are influenced by oxidative stress, and the NF-κB/P53 signaling pathway is implicated. These findings provide preliminary evidence that stem cells and their exosomes may not be suitable for patients with tumor diseases, offering an experimental basis for the potential clinical application safety of this technology in treatment. [ES] Antecedentes: Las células madre mesenquimales del cordón umbilical (UCMSCs) se derivan del tejido del cordón umbilical. Debido a su baja inmunogenicidad, fácil disponibilidad, tecnología de cultivo madura y falta de controversia ética, se han convertido gradualmente en un punto focal en la investigación con células madre. Los exosomas son vesículas derivadas de células con una estructura consistente con la membrana celular, que funcionan principalmente como portadores de sustratos de transporte para la comunicación y regulación intercelular. En la actualidad, tanto las células madre como sus exosomas se han convertido en productos biofarmacéuticos muy prometedores ampliamente utilizados en diversos estudios clínicos, como la cicatrización de heridas, las lesiones de la médula espinal, la rehabilitación postoperatoria, los trastornos neurológicos y las enfermedades autoinmunes. Sin embargo, la seguridad de estos productos biológicos sigue siendo incierta, y algunos estudios sugieren la posible tumorigénesis de las células madre y sus exosomas. El objetivo de este estudio fue investigar los efectos de las UCMSCs y sus exosomas en cuatro tipos de células tumorales. Métodos: En este estudio, en primer lugar, se aislaron y caracterizaron las UCMSC y sus exosomas. Posteriormente, el estudio se realizó en experimentos celulares. Los efectos de las UCMSC y sus exosomas en cuatro tipos de células tumorales (línea celular de cáncer de blasto, línea celular de cáncer gástrico, línea celular de glioma y línea celular de cáncer de pulmón) se observaron a través de experimentos de cocultivo. Los observables incluyeron los efectos sobre el fenotipo in vitro y las características de crecimiento in vivo. Los cambios en la expresión génica se analizaron utilizando tecnología de secuenciación de alto rendimiento para dilucidar las funciones biológicas y los roles de las UCMSC y sus exosomas en las células tumorales. Resultados: Las UCMSC fueron exitosamente aisladas, cultivadas e identificadas. Demostraron la capacidad de diferenciación en adipocitos, osteoblastos, condrocitos y células similares a neuronas, lo que indica su potencial de diferenciación multilinaje. Los UCMSCs-exos exhibieron un diámetro que varió de 30 a 150 nm, con un tamaño promedio de 126.62 ± 1.64 nm, y mostraron una mayor expresión de las proteínas Tsg101, CD9 y CD63 (P 0,05). Sin embargo, en las células LN-229, los niveles de ROS y MDA se redujeron, y los niveles de SOD aumentaron en el grupo de UCMSCs en comparación con el grupo de UCMSCs-exos (P < 0,05). Además, las UCMSCs y las UCMSCs-exos no afectaron la expresión de las proteínas NF- κB y p53 en las células MDA-MB-231, BGC-823 y A549 (P > 0,05). Por el contrario, inhibieron la expresión de las proteínas NF-κB y p53 en LN-229, y las UCMSCs-exos demostraron un efecto inhibidor más pronunciado (P < 0,05). Conclusiones: En conclusión, este estudio aisló con éxito las UCMSC y sus exosomas. Promueven la proliferación, migración e invasión de cuatro tipos de células tumorales que implican la alteración del ciclo celular. Además, las UCMSC y sus vesículas extracelulares están influenciadas por el estrés oxidativo, y la vía de señalización NF-κB/P53 está implicada. Estos hallazgos proporcionan evidencia preliminar de que las células madre y sus exosomas pueden no ser adecuados para pacientes con enfermedades tumorales, ofreciendo una base experimental para la posible seguridad de la aplicación clínica de esta tecnología en el tratamiento

Extracellular Vesicles: Biology and Potentials in Cancer Therapeutics

Extracellular vesicles (EVs) are particles wrapped in a lipid bilayer membrane and are naturally released from cells. This kind of cargo vessel is a nanostructure that mainly transfers lipids, proteins, various nucleic acid fragments, and metabolic components to neighboring cells or distant parts of the body through the circulatory system. EVs are of great significance to the communication mechanism between cells. This book collects feature articles to enhance our understanding of the biological characteristics of EVs and their potential applications

Cancer Nanomedicine

This special issue brings together cutting edge research and insightful commentary on the currentl state of the Cancer Nanomedicine field

Advances in Nanomaterials in Biomedicine

Advances in Nanomaterials in Biomedicine” provided a platform for more than 110 researchers from different countries to present their latest investigations in various fields of nanotechnology, new methods and nanomaterials intended for medical applications. Modern achievements in the field of nanoparticle-based diagnostics, drug delivery and the use of various nanomaterials in the treatment of diseases are presented in 11 original articles. The published reviews provide a comprehensive analysis of the current information on the use of nanomedicine in the treatment and diagnosis of cancer and liver fibrosis, in the field of solid tissue engineering and in drug delivery systems

Extracellular vesicles in gastric cancer: role of exosomal lncRNA and microRNA as diagnostic and therapeutic targets

Extracellular vesicles (EVs), including exosomes, play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of gastric cancer. This review discusses the current understanding of the role of EVs, particularly exosomal lncRNA and microRNA, in gastric cancer and their potential as diagnostic and therapeutic targets. Exosomes are small membrane-bound particles secreted by both cancer cells and stromal cells within the tumor microenvironment. They contain various ncRNA and biomolecules, which can be transferred to recipient cells to promote tumor growth and metastasis. In this review, we highlighted the importance of exosomal lncRNA and microRNA in gastric cancer. Exosomal lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. We also discuss the potential use of exosomal lncRNAs and microRNAs as diagnostic biomarkers for gastric cancer. Exosomes can be isolated from various bodily fluids, including blood, urine, and saliva. They contain specific molecules that reflect the molecular characteristics of the tumor, making them promising candidates for non-invasive diagnostic tests. Finally, the potential of targeting exosomal lncRNAs and microRNAs as a therapeutic strategy for gastric cancer were reviewed as wee. Inhibition of specific molecules within exosomes has been shown to suppress tumor growth and metastasis in preclinical models. In conclusion, this review article provides an overview of the current understanding of the role of exosomal lncRNA and microRNA in gastric cancer. We suggest that further research into these molecules could lead to new diagnostic tools and therapeutic strategies for this deadly disease