\u201cINVESTIGATING THE EFFECT OF SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES ON HYPERPROLIFERATIVE CELLULAR MODEL DISEASE\u201d

The growing impact of nanotechnology in the field of medicine as a new potential clinical therapeutic agent requires the joint efforts of interdisciplinary research groups. Numerous questions must be faced. The main issues to be considered involve the mechanisms of interaction with the cells before, during and after their adhesion and internalization, the degradation pathways, cytotoxicity and the therapeutic efficacy. For these reasons, I attended to the construction of superparamagnetic iron oxide nanoparticles capable of providing compelling evidence of any of the abovedescribed key factors. To assess the utility of these nanoparticles, I chose to treat obesity and glioblastoma as two hyperproliferative disease models, which affect millions of adult every year worldwide. An attractive innovative possibility to approach the hyperproliferation can be envisaged in developing heating agents via magnetic nanoparticles. Thanks to their unique magnetic properties, superparamagnetic iron oxide nanoparticles now find large application as heating mediators for thermotherapy. These nanoparticles need to fulfil several criteria in order to be used as therapeutic agents in humans, including nontoxicity, heating efficiency and sensitivity of detection resulting in a capability of the nanoparticles to be confined preferentially at the diseased site. It is common believed in fact that alternative factors, including opsonisation, macrophage-mediated transport and passive delivery in general, might strongly affect the targeting efficiency and final destiny of nanoparticles. Using magnetic nanoparticles coated with protein-targeting biomarkers overexpressed by targeted tissue may be provided these factors. So the last step of the present work was focused on the construct of a peptidenanoconjugate to perform an accurate study of nanoparticle-membrane receptor in vivo. In summary, the general scope of this thesis was to develop an efficient nanoparticle for the investigation of the effect of thermotherapy mediated by magnetic nanoparticles on two hyperproliferative diseases. Several issues including nanoparticles synthesis, bio-functionalization, toxicity and the use as therapeutic agents have been thoroughly examinated and optimized. By taking advantage of the interdisciplinary view offered by synergistic chemical, 9 physical and biochemical approaches, I have designed a new nano-system suitable to explore new frontiers in the therapy of the hyperproliferative diseases. Of course, the clinical application in human treatments is the final goal of this and its related research. However, to reach such objective is necessary not only to design a suitable system for practical use, but also to assess and optimize the essential characteristics for specific effects such as safety, capability to get to the specific target, to provide useful signal amplification and to avoid the immunogenic system

Hyperthermic superparamagnetic nanoparticles modulate adipocyte metabolism

Adipocytes are the principal cellular component in adipose tissue and their excessive hyperplasia or hypertrophy is actively involved in regulating physiologic and pathologic processes such as inflammation, cardiovascular disease, obesity and tumour. The main depot of energy in adipocytes is represented by lipid droplets, intracellular organelles that play fundamental roles in regulation of metabolic processes. An accumulation of such droplets could be a potential biomarker of disease caused by metabolic dysregulation. Recent studies have demonstrated that heat shock is associated with alteration in energy metabolism: the aim of this study is to modulate the energy metabolism of the adipocytes via controlled administration of thermal energy to reduce the number of lipid droplets. We have investigated the effect of controlled heating of adipocytes using an alternating magnetic field (AMF) on samples loaded with superparamagnetic nanoparticles (MNP) as heating agent

Detection of nanostructures in solutions of Zincum metallicum and the vehicle lactose

Background: Nanoparticles (NP), because of their size (< 1μm) and high relative surface area, are highly reactive forms of their source material with biological, chemical, optical, electromagnetic, and thermal properties different from larger bulk forms of the same material. It has been speculated that NPs can occur in homeopathic products as a function of trituration and shaking into glass containers. Moreover, the presence of sugars additives like lactose and of silicates leaked from the glassware are reported to stabilize the nanoparticles.1 Up to now some authors observed nanoparticles in highly diluted samples2, 3, but further studies are needed to know the nature of the NPs. Actually, nanostructures in the solutions may derive from the source materials but also from stuff contaminations and also may be constituted by nano-bubbles.4, 5 Moreover, the mechanism by which the nanostructures can be formed and the effect of serial dilution/succussions of the NPs suspension should be studied.6 Many tools are available to analyze the nanostructures both in solutions or in dried samples and these give complementary information about the concentration, stability, structure and chemical nature of the NPs. In the present report we describe preliminary observations obtained by the nanoparticle tracking analysis (NTA) in Zincum metallicum (Zinc met.) solutions at low-grade dilution/dynamization and their lactose controls. This study is part of a formal Brazilian-Italian inter-university collaboration

Magnetosomes Extracted from Magnetospirillum gryphiswaldense as Theranostic Agents in an Experimental Model of Glioblastoma

Magnetic fluid hyperthermia (MFH) with chemically synthesized nanoparticles is currently used in clinical trials as it destroys tumor cells with an extremely localized deposition of thermal energy. In this paper, we investigated an MFH protocol based on magnetic nanoparticles naturally produced by magnetotactic bacteria: magnetosomes. The efficacy of such protocol is tested in a xenograft model of glioblastoma. Mice receive a single intratumoral injection of magnetosomes, and they are exposed three times in a week to an alternating magnetic field with concurrent temperature measurements. MRI is used to visualize the nanoparticles and to monitor tumor size before and after the treatment. Statistically significant inhibition of the tumor growth is detected in subjects exposed to the alternating magnetic field compared to control groups. Moreover, thanks to magnetosomes high transversal relaxivity, their effective delivery to the tumor tissue is monitored by MRI. It is apparent that the efficacy of this protocol is limited by inhomogeneous delivery of magnetosomes to tumor tissue. These results suggest that naturally synthesized magnetosomes could be effectively considered as theranostic agent candidates for hyperthermia based on iron oxide nanoparticles

Hyperthermic nanocarriers for biomedical applications

Hyperthermic nanocarriers have been used for different biomedical application

Innovative approach to safely induce controlled lipolysis by superparamagnetic iron oxide nanoparticles-mediated hyperthermic treatment

During last years, evidence has been provided on the involvement of overweight and obesity in the pathogenesis and aggravation of several life-threatening diseases. Here, we demonstrate that, under appropriate administration conditions, polyhedral iron oxide nanoparticles are efficiently and safely taken up by 3T3 cell line-derived adipocytes (3T3 adipocytes) in vitro. Since these nanoparticles proved to effectively produce heat when subjected to alternating magnetic field, 3T3 adipocytes were submitted to superparamagnetic iron oxide nanoparticles-mediated hyperthermia treatment (SMHT), with the aim of modulating their lipid content. Notably, the treatment resulted in a significant delipidation persisting for at least 24h, and in the absence of cell death, damage or dedifferentiation. Interestingly, transcript expression of adipose triglyceride lipase (ATGL), a key gene involved in canonical lipolysis, was not modulated upon SMHT, suggesting the involvement of a novel/alternative mechanism in the effective lipolysis observed. By applying the same experimental conditions successfully used for 3T3 adipocytes, SMHT was able to induce delipidation also in primary cultures of human adipose-derived adult stem cells. The success of this pioneering approach in vitro opens promising perspectives for the application of SMHT in vivo as an innovative safe and physiologically mild strategy against obesity, potentially useful in association with balanced diet and healthy lifestyle

Antiproliferative Effect of ASC-J9 Delivered by PLGA Nanoparticles against Estrogen-Dependent Breast Cancer Cells

Among polymeric nanoparticles designed for cancer therapy, PLGA nanoparticles have become one of the most popular polymeric devices for chemotherapeutic-based nanoformulations against several kinds of malignant diseases. Promising properties, including long-circulation time, enhanced tumor localization, interference with “multidrug” resistance effects, and environmental biodegradability, often result in an improvement of the drug bioavailability and effectiveness. In the present work, we have synthesized 1,7-bis­(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one (ASC-J9) and developed uniform ASC-J9-loaded PLGA nanoparticles of about 120 nm, which have been prepared by a single-emulsion process. Structural and morphological features of the nanoformulation were analyzed, followed by an accurate evaluation of the <i>in vitro</i> drug release kinetics, which exhibited Fickian law diffusion over 10 days. The intracellular degradation of ASC-J9-bearing nanoparticles within estrogen-dependent MCF-7 breast cancer cells was correlated to a time- and dose-dependent activity of the released drug. A cellular growth inhibition associated with a specific cell cycle G2/M blocking effect caused by ASC-J9 release inside the cytosol allowed us to put forward a hypothesis on the action mechanism of this nanosystem, which led to the final cell apoptosis. Our study was accomplished using Annexin V-based cell death analysis, MTT assessment of proliferation, radical scavenging activity, and intracellular ROS evaluation. Moreover, the intracellular localization of nanoformulated ASC-J9 was confirmed by a Raman optical imaging experiment designed <i>ad hoc</i>. PLGA nanoparticles and ASC-J9 proved also to be safe for a healthy embryo fibroblast cell line (3T3-L1), suggesting a possible clinical translation of this potential nanochemotherapeutic to expand the inherently poor bioavailability of hydrophobic ASC-J9 that could be proposed for the treatment of malignant breast cancer

Politiche professionali: studio qualitativo sulle percezioni e le opinioni dei professionisti infermieri/ostetriche e degli studenti della Laurea magistrale in Scienze infermieristiche e ostetriche.

Introduzione. La politica, ovvero la scienza e l'arte di amministrare la cosa pubblica, è un ambito di grande importanza e occuparsi di politica professionale significa dedicarsi al bene della professione. Le politiche professionali sono parte integrante del prendersi cura e la famiglia professionale ha bisogno di punti chiari di riferimento: formazione, tutela, promozione, rappresentanza istituzionale.Obiettivo. Esplorare percezioni, idealití , immaginario condiviso e desideri circa le politiche professionali di infermieri/ostetriche e studenti della laurea magistrale per riuscire ad avere una rappresentazione della realtí  e avviare una riflessione critica sul tema. Metodo. È stato effettuato uno studio qualitativo su un campione propositivo di 22 professionisti infermieri/ostetriche quali testimoni qualificati della situazione nazionale. I dati sono stati raccolti attraverso un questionario costruito ad hoc.Risultati. Dall'analisi delle risposte sono emersi 10 temi principali, tra i quali spiccano: per la formazione l'importanza delle nuove conoscenze ma anche la scarsa differenziazione dei ruoli; per l'ambito lavorativo l'assenza di meritocrazia e di nuove opportunití ; per la ricerca il divario tra teoria e pratica. In sintesi, i risultati evidenziano come la partecipazione ai processi di formazione delle politiche sia saltuaria e di poca intensití  e come pochi infermieri/ostetriche siano coinvolti attivamente per la promozione e sviluppo di progetti nel settore delle politiche per i sistemi sanitari e per la salute.Conclusioni. L'indagine rileva che vi è una coscienza forte delle problematicití  esistenti, ma questa coscienza non sembra relazionarsi adeguatamente ai contesti lavorativi, istituzionali e culturali. Di conseguenza non si verifica quella necessaria crescita delle politiche professionali, la sola capace di generare percorsi politici atti a risolvere le questioni di fondo. Parole chiave: politica sanitaria, partecipazione politica, infermieri/ostetriche, leadership politica.Professional policies: a qualitative study of perceptions and opinions of professionals nurses/midwives and students attending the Master of Science in NursingABSTRACTIntroduction. Politics, the science and the art of administering public affairs, is a very important field. Dealing with professional policy means to dedicate ourselves to the good of the profession. Professional policies are an integral part of taking care; the professional family needs clear reference points: training, tutoring, promotion and institutional representation.Aim. Exploring perceptions, ideals, shared imagination and desires about the professional policies of nurses/midwives and of master's students in order to be able to have a representation of the reality and to start a critical reflection on the subject. Method. A qualitative study was conducted on a proactive sample of 22 nurses / midwives as qualified witnesses of the national situation. The data was collected through a questionnaire built ad hoc.Results.  From the analysis of the answers given to the questionnaire, we identified 10 main themes. In the training sector two of the themes that were selected are the importance of the new knowledges and inadequate differentiation of the positions; Regarding the working sector two of the themes that came out are the lack of meritocracy and of new opportunities; meanwhile, in the research field one of the main theme identified is the gap between the theory and the practice.Conclusions.  The present study finds out that participation in policy-making processes is occasional and of little intensity: just few nurses/midwives are actively involved in the promotion and development of projects in the health sector and of healthcare policies. Keywords: health policy, political participation, nurses/midwiferies, political leadership