Magnetic molecularly imprinted polymers for breast cancer cell targeting and drug delivery under alternative magnetic field

Les nanoparticules connaissent actuellement un essor important de leur utilisation pour des application biomédicales. Leurs propriétés en font des objets de choix, tant pour le développement de nouvelles méthodes de diagnostic que pour une utilisation comme vecteurs thérapeutiques. De nombreuses pathologies peuvent bénéficier de l’utilisation de vecteurs pour transporter des molécules thérapeutiques en particulier lorsque la cible thérapeutique est difficile d’accès, pour augmenter l’efficacité d’un médicament ou diminuer les effets secondaires qui lui sont associés. Les stratégies thérapeutiques pour lutter contre le cancer impliquent souvent des molécules présentant une forte toxicité systémique qu'il est donc nécessaire de diriger spécifiquement vers la tumeur, tout en protégeant le reste de l’organisme du patient. En plus du contrôle de la destination du vecteur, la maîtrise du mécanisme de libération de la molécule thérapeutique est essentielle pour obtenir un vecteur efficace. Le cancer du sein est le cancer le plus diagnostiqué et le plus mortel chez la femme. En particulier, les tumeurs dites triples négatives sont de mauvais pronostic en raison du nombre restreint de stratégies thérapeutiques efficaces. Parmi les nouvelles pistes explorées, l’étude de la communication entre les cellules tumorales et leur microenvironnement, et en particulier le tissu adipeux, a montré que ce dernier sécrète des composés induisant une augmentation des métastases et des résistances aux traitements. Le transporteur d’acides gras CD36 a été associé à ces mécanismes, ce qui en fait une cible intéressante pour contrer ce phénomène et améliorer le pronostic des patientes. L’objectif de ce projet est de développer de nouveaux vecteurs thérapeutiques capables de cibler la protéine CD36 et d’induire la libération contrôlée d’une molécule thérapeutique dans le but de diminuer le potentiel métastatique des tumeurs et les résistances aux traitements. Pour permettre d’induire la libération d’une molécule, des nanoparticules superparamagnétiques d’oxyde de fer, capables de produire de la chaleur en présence d’un champ magnétique alternatif, ont été choisies pour former le cœur du vecteur. La stratégie permettant de cibler la protéine CD36 consiste quant à elle à former des empreintes dans une matrice de polymère en utilisant la technologie des polymères à empreintes moléculaires.The use of nanoparticles for biomedical applications is currently increasing. Their properties make them perfect objects, both for the development of new diagnostic methods and as therapeutic vectors. Numerous pathologies can benefit from the use of vectors to transport therapeutic molecules, particularly when their target is difficult to access, to increase the efficacy of a drug or to reduce its associated side effects. Therapeutic strategies to fight cancer often involve molecules with high systemic toxicity that needs to by directed to the tumor, in order to protect the rest of the patient's body. In addition to controlling the vector's destination, mastery of the therapeutic molecule's delivery mechanism is essential to obtain an effective vector. Breast cancer is the most frequently diagnosed and lethal cancer in women. In particular, so-called triple-negative tumors have a poor prognosis due to the limited number of effective therapeutic strategies. Among the new strategies explored, the study of communication between tumor cells and their microenvironment, and in particular adipose tissue, has shown that the latter secretes compounds that induce increased metastasis and resistance to treatment. The fatty acid transporter CD36 has been associated with these mechanisms, making it an interesting target for countering this phenomenon and improving patient prognosis. The aim of this project is to develop new therapeutic vectors capable of targeting the CD36 protein and inducing the controlled release of a therapeutic molecule, with the aim of reducing the metastatic potential of tumors and treatment resistance. To induce the release of the therapeutic molecule, superparamagnetic iron oxide nanoparticles, capable of generating heat in the presence of an alternating magnetic field, were chosen as the core of the vector. The strategy for targeting the CD36 protein is to form imprints in a polymer matrix using molecularly imprinted polymer technology

Hybrid Molecularly Imprinted Polymers: The Future of Nanomedicine?

International audienceMolecularly imprinted polymers (MIPs) have been widely used in nanomedicine in the last few years. However, their potential is limited by their intrinsic properties resulting, for instance, in lack of control in drug release processes or complex detection for in vivo imaging. Recent attempts in creating hybrid nanomaterials combining MIPs with inorganic nanomaterials succeeded in providing a wide range of new interesting properties suitable for nanomedicine. Through this review, we aim to illustrate how hybrid molecularly imprinted polymers may improve patient care with enhanced imaging, treatments, and a combination of both

One‐Step Synthesis of Fluorescent Poly(divinylbenzene) Particles without Fluorescent Monomers

A simple and cost-efficient method for fluorescent microsphere synthesis, which does not require any fluorescent monomers or modification steps to incorporate fluorescent moieties into the polymer particles, is reported. Using rhodamine B and benzophenone as bimolecular initiation system in type II photoinitiated precipitation polymerization, the method enables the preparation of fluorescent microspheres in one step, at room temperature and without the need for a stabilizer or surfactant of any type

Detection of Anaplasma and Ehrlichia bacteria in humans, wildlife, and ticks in the Amazon rainforest.

International audienceTick-borne bacteria of the genera Ehrlichia and Anaplasma cause several emerging human infectious diseases worldwide. In this study, we conduct an extensive survey for Ehrlichia and Anaplasma infections in the rainforests of the Amazon biome of French Guiana. Through molecular genetics and metagenomics reconstruction, we observe a high indigenous biodiversity of infections circulating among humans, wildlife, and ticks inhabiting these ecosystems. Molecular typing identifies these infections as highly endemic, with a majority of new strains and putative species specific to French Guiana. They are detected in unusual rainforest wild animals, suggesting they have distinctive sylvatic transmission cycles. They also present potential health hazards, as revealed by the detection of Candidatus Anaplasma sparouinense in human red blood cells and that of a new close relative of the human pathogen Ehrlichia ewingii , Candidatus Ehrlichia cajennense, in the tick species that most frequently bite humans in South America. The genome assembly of three new putative species obtained from human, sloth, and tick metagenomes further reveals the presence of major homologs of Ehrlichia and Anaplasma virulence factors. These observations converge to classify health hazards associated with Ehrlichia and Anaplasma infections in the Amazon biome as distinct from those in the Northern Hemisphere

Work-related asthma in France: Recent trends for the period 2001-2009

Objective: Knowledge on the time-course (trends) of work-related asthma (WRA) remains sparse. The aim of this study was to describe WRA trends in terms of industrial activities and the main causal agents in France over the period 2001-2009. Method: Data were collected from the French national network of occupational health surveillance and prevention (Réseau National de Vigilance et de Prévention des Pathologies Professionnelles (RNV3P)). Several statistical models (non-parametric test, zero-inflated negative binomial, logistic regression and time-series models) were used and compared with assess trends. Results: Over the study period, 2914 WRA cases were included in the network. A significant decrease was observed overall and for some agents such as isocyanates (p=0.007), aldehydes (p=0.01) and latex (p=0.01). Conversely, a significant increase was observed for cases related to exposure to quaternary ammonium compounds (p=0.003). The health and social sector demonstrated both a growing number of cases related to the use of quaternary ammonium compounds and a decrease of cases related to aldehyde and latex exposure. Conclusions: WRA declined in France over the study period. The only significant increase concerned WRA related to exposure to quaternary ammonium compounds. Zero-inflated negative binomial and logistic regression models appear to describe adequately these data

Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study

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The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

International audienceAbstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I 2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup