Nanodispositivos magnéticos y termosensibles : síntesis, estudios de sus propiedades físico-químicas y potencial aplicación en nanomedicina

Tesis (Doctora en Ciencias Químicas) - - Universidad Nacional de Córdoba. Facultad de Ciencias Químicas, 2017Resumen: La nanomedicina busca superar nuevos desafíos y problemas que enfrenta la medicina convencional como la toxicidad sistémica y efectos adversos de los agentes anticancerígenos disponibles en la actualidad. Ambas disciplinas son responsables del diagnóstico, tratamiento, prevención de enfermedades, y del alivio del paciente mejorando su calidad de vida. En las terapias convencionales, las moléculas de fármacos simplemente se difunden y distribuyen libremente en todo el cuerpo causando así, efectos secundarios indeseables y limitando el uso de la dosis máxima para un tratamiento eficaz. Con el fin poder superar las limitaciones asociadas con las formulaciones convencionales de fármacos, surge el concepto y la implementación de nanodispositivos y nanotransportadores. Estos tienen el potencial de modular tanto los perfiles farmacocinéticos como farmacodinámicos de los medicamentos mejorando de esta manera su índice terapéutico. Consecuentemente, su incorporación en nanodispositivos puede incrementar su estabilidad in vivo, extender su tiempo de circulación sanguínea y permitir la liberación controlada de los mismos en un sitio determinado. En este contexto, se ubica el presente trabajo de Tesis Doctoral titulado: “NANODISPOSITIVOS MAGNÉTICOS Y TERMOSENSIBLES: síntesis, estudios de sus propiedades físico-químicas y potencial aplicación en nanomedicina”. Este trabajo tiene como objetivo principal el diseño racional de nanodispositivos híbridos, formados con nanopartículas magnéticas de óxido de hierro y un polímero termosensible, mediante el empleo de una metodología de síntesis novedosa como es la síntesis asistida por ultrasonicación. En la tesis doctoral se describe la síntesis de distintos nanodispositivos con el fin de obtener dos morfologías diferentes: nanogeles híbridos, en los que las nanopartículas magnéticas(MNPs) están unidas químicamente a una red tridimensional polimérica y del tipo corebrush, siendo el corazón la MNP con cadenas poliméricas unidas covalentemente a su superficie. El objetivo de este estudio es la obtención de nanogeles híbridos y nanopartículas magnéticas core-brush para su potencial aplicación en nanomedicina. Para ello, se desarrolló una nueva metodología de síntesis de distintos sistemas empleando ultrasonicación. Consecuentemente, se demostró el potencial que presenta esta metodología como herramienta de síntesis no sólo de nanogeles y nanopartículas core-brush sino también, para la modificación superficial de nanopartículas con diferentes agentes silano. En una primera etapa, en el estudio de los nanogeles, se evaluó la síntesis de nanogeles termosensibles mediante polimerización radicalaria no controlada; para poder luego, estudiar la incorporación de nanopartículas magnéticas de manera covalente a los fines de obtener nanogeles magnéticos y termosensibles. Los mismos presentaron alta estabilidad coloidal en el tiempo, comportamiento termosensible que puede ser controlado a partir de las condiciones de síntesis, propiedades superparamagnéticas y respuesta a irradiación de infrarrojo cercano (NIR) enfatizando su potencial uso para el tratamiento por hipertermia, así como tiempos de relajación similares a los agentes comerciales utilizados en la actualidad en resonancia magnética de imágenes. Por otro lado, se estudió la síntesis de nanogeles magnéticos y termosensibles mediante química click y nanoprecipitación asistida por ultrasonicación obteniendo resultados prometedores similares a los expuestos para los nanogeles magnéticos sintetizados vía polimerización radicalaria. Además, se evaluó la potencial aplicación de los mismos en el campo de la nanomedicina. Se demostró la factibilidad del empleo de estos sistemas tanto para liberación controlada de fármacos, así como también para la captura de células circulantes de metástasis. En una segunda etapa, se estudió la síntesis de nanopartículas magnéticas tipo corebrush mediante polimerización radicalaria por transferencia atómica (ATRP) y mediante química click. Aquellas nanopartículas sintetizadas mediante esta última técnica demostraron tener potencial aplicación en el campo de la liberación controlada de fármacos. La Tesis ha sido organizada en cinco secciones. La primera consta de la introducción y los objetivos generales. En ésta se desarrollan conceptos relacionados a la temática abordada ofreciendo una revisión de los principales antecedentes para luego plantear la motivación y los objetivos de este trabajo. En la segunda sección, Materiales y Métodos, se encuentra detallado el desarrollo experimental utilizado para este trabajo de tesis. La tercera y cuarta sección presentan el estudio de cada uno de los sistemas desarrollados. Finalmente, la quinta parte contiene las consideraciones finales de este trabajo. A su vez, cada una de dichas secciones está dividida en capítulos, con su introducción, objetivos específicos, desarrollo y conclusiones. El desarrollo de esta Tesis de Doctorado fue posible debido a la colaboración y al trabajo conjunto de investigadores de distintas áreas. Este estudio se destacó por su carácter multi e interdisciplinario y por ser uno de los primeros antecedentes en el Laboratorio de Materiales Poliméricos (LaMaP) en la investigación de nanomateriales mediante la síntesis asistida por ultrasonicación y la síntesis de nanogeles híbridos termosensibles.Abstract: One of the main goals of nanomedicine is to overcome the challenges and problems that conventional medicine presents. Both disciplines comprise the diagnosis, treatment and prevention of diseases, as well as the patient relief improving their life quality. In conventional therapies, drug molecules simply diffuse and distribute freely throughout the body thus causing undesirable side effects and limiting the use of the dose required for effective treatment. In order to overcome the pharmacokinetic limitations associated with conventional drug formulations, concepts such as nanodevices and nanocarriers emerged. These systems have the potential to modulate both pharmacokinetic and pharmacodynamic drug profiles thus improving their therapeutic index. Therefore, incorporation of drugs into nanodevices may increase their stability in vivo, extend their blood circulation time and allow controlled release of the drug at a given site. In this context, the present PhD thesis entitled: ‘MAGNETIC AND THERMORESPONSIVE NANODEVICES: Synthesis, studies of their physicochemical properties and potential applications in nanomedicine’ was carried out. This work had as main objective the rational design of hybrid nanodevices, formed by iron oxide magnetic nanoparticles and a thermoresponsive polymer using a novel ultrasound assisted synthetic methodology. This thesis describes the synthesis of different nanodevices with two different morphologies: hybrid nanogels, in which MNPs are chemically linked to a three-dimensional polymer network and core-brush nanoparticles, in which the MNP is the core and polymer chains are attached to their surface by covalent bonds. The main goal of this study was to obtain hybrid nanogels and core-brush magnetic nanoparticles for their potential application in nanomedicine. For this purpose, a new synthetic methodology of different systems was developed using ultrasonication. The methodology established was a key tool of great importance for this work, since it allows the synthesis of not only nanogels and core-brush nanoparticles but also nanoparticles surface modification with different silane agents. In a first stage, nanogels synthesis was studied. To begin with, ultrasound assisted synthesis of thermoresponsive nanogeles was evaluated using free radical polymerization; then we studied the covalent incorporation of magnetic nanoparticles to obtain magnetic and thermoresponsive nanogels. These systems showed high colloidal stability over time, thermoresponsive behavior that can be controlled with the conditions of synthesis, and superparamagnetic properties and response to near-infrared irradiation (NIR) which emphasize their potential use in hyperthermia treatment. Furthermore, nanogels presented relaxation times similar to the commercial magnetic agents for magnetic resonance imaging allowing their use in diagnosis. Afterwards, we studied ultrasound assisted synthesis of magnetic and thermoresponsive nanogels obtained by click chemistry and nanoprecipitation. We obtained promising results like those presented for magnetic nanogels synthesized via radical polymerization. In addition, the potential application of nanomedicine in the field of nanomedicine was evaluated. Potential use of these nanogels was demonstrated for both controlled release of drugs as well as capture of circulating metastatic cells. In a second stage, the synthesis of magnetic core-brush nanoparticles was studied. We analyzed different synthetic methodologies such as atomic transfer radical polymerization (ATRP) and click chemistry. Those nanoparticles synthesized by this last methodology showed a potential application in the field of controlled drug release. This Thesis has been organized in five sections. The first part consists of the introduction and general objective, developing the concepts related to the topic addressed and the state of art in this field, following by problem statement and motivation of the research. In Part 2, Materials and Methods, the experimental development used for this thesis work is detailed. Then parts 3 and 4 describe all studied systems. Finally, Part 5 presents the final conclusions of this work. Besides, each of these sections is divided into chapters, with their introduction and specific objectives, discussion and conclusions. The accomplishment of this doctoral thesis has been possible due to the collaboration and joint work between researchers from different areas. The development of this Thesis stands out for its multi and interdisciplinary nature and for being one of the first antecedents in the Laboratory of Polymeric Materials (LaMaP) in the study of nanomaterials through the ultrasound assisted synthesis of hybrids materials.Fil: Strumia, Miriam Cristina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina.Fil: Strumia, Miriam Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación y Desarrollo en Ingeniería de Procesos; Argentina.Fil: Biglione, Catalina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Giacomelli, Carla Eugenia. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Físico química; Argentina.Fil: Giacomelli, Carla Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico química de Córdoba; Argentina.Fil: Lacconi, Gabriela Inés. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Fisicoquímica; Argentina.Fil: Lacconi, Gabriela Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Fisicoquímica de Córdoba; Argentina.Fil: Pacioni, Natalia Lorena. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina.Fil: Pacioni, Natalia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Fisicoquímica de Córdoba; Argentina.Fil: Williams, Federico J. Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil: Williams, Federico J. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Física de los Materiales, Medio Ambiente y Energía; Argentina

Design, Synthesis and Architectures of Hybrid Nanomaterials for Therapy and Diagnosis Applications

Hybrid nanomaterials based on inorganic nanoparticles and polymers are highly interesting structures since they combine synergistically the advantageous physical-chemical properties of both inorganic and polymeric components, providing superior functionality to the final material. These unique properties motivate the intensive study of these materials from a multidisciplinary view with the aim of finding novel applications in technological and biomedical fields. Choosing a specific synthetic methodology that allows for control over the surface composition and its architecture, enables not only the examination of the structure/property relationships, but, more importantly, the design of more efficient nanodevices for therapy and diagnosis in nanomedicine. The current review categorizes hybrid nanomaterials into three types of architectures: core-brush, hybrid nanogels, and core- shell. We focus on the analysis of the synthetic approaches that lead to the formation of each type of architecture. Furthermore, most recent advances in therapy and diagnosis applications and some inherent challenges of these materials are herein reviewed

Two Cu-Based Phosphonate Metal-Organic Frameworks as Efficient Water-Splitting Photocatalysts

[EN] Two novel three-dimensional metal-organic frameworks(MOFs)based on the photoactive pyrene tetraphosphonate ligand and copper(denoted as IEF-8 and IEF-9) have been hydrothermally synthesizedand fully characterized (XRD, FTIR, TGA, SEM, XPS, etc.). Their crystalstructures were unveiled by single-crystal X-ray diffraction. Remarkably,these materials exhibit coordinatively unsaturated copper (II) sites,free -PO3H2 and -PO3H acidic groups, and good thermal and chemical stability. Further,their optoelectronic characterization evidenced a photoresponse suitablefor photocatalysis. In this sense, the photocatalytic activity ofpyrene phosphonate MOFs was evaluated for the first time for the challenginghydrogen evolution reaction. In particular, IEF-8 exhibited a catalyticefficiency higher than that of the benchmarked Ti carboxylate photocatalystMIL-125-(Ti)-NH2, producing 1800 mu mol center dot g(-1) after 22 h under UV-vis irradiation in theabsence of any co-catalyst. Furthermore, this material presented goodreusability (at least up to 4 cycles), preserving its activity andstructural integrity.The authors acknowledge the Maria de Maeztu IMDEA Energy Institute, the M-ERA-NET C-MOF-cell project, the Retos Investigacion MOFSEIDON project (PID2019-104228RB-I00 funded by MCIN/AEI/10.13039/501100011033 and by the European Union, MICIU-AEI/FEDER, UE), and the H2-MOF project (TED2021-132092B-C21 funded by MCIN/AEI/10.13039/501100011033 and by the European Union NextGenerationEU/PRTR). They thank "Comunidad de Madrid" and European Regional Development Fund-FEDER 2014-2020-OE REACT-UE 1for their financial support to the VIRMOF-CM project associated to R & D projects in response to COVID-19. S.N. thanks the support of grant PID2021-123856OBI00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe.Salcedo-Abraira, P.; Serrano Nieto, R.; Biglione, C.; Cabrero-Antonino, M.; Vilela, SM.; Babaryk, AA.; Tilve-Martínez, D.... (2023). Two Cu-Based Phosphonate Metal-Organic Frameworks as Efficient Water-Splitting Photocatalysts. Chemistry of Materials. 35(11):4211-4219. https://doi.org/10.1021/acs.chemmater.3c0005442114219351

Amphiphilic micro- and nanogels: Combining properties from internal hydrogel networks, solid particles, and micellar aggregates

Polymeric micro- and nanogels are defined by their water-swollen hydrophilic networks that can often impart outstanding biocompatibility and high-colloidal stability. Unfortunately, this highly hydrophilic nature limits their potential in areas where hydrophobic or amphiphilic interactions are required, for example, the delivery of hydrophobic cargoes or tailored interactions with amphipathic (bio-)surfaces. To overcome this limitation, amphiphilic micro−/nanogels are emerging as new colloidal materials that combine properties from hydrogel networks with hydrophobic segments, known from solid hydrophobic polymer particles or micellar cores. The ability to accurately adjust the balance of hydrophobic and hydrophilic components in such amphiphilic colloidal systems enables new tailored properties. This opens up new applications ranging from the controlled and sustained delivery of hydrophobic drugs, over carriers for catalytic moieties, to their assembly at hydrophilic/hydrophobic interfaces, for example, as advanced stabilizers in Pickering emulsions. While promising, the synthetic realization of such amphiphilic materials remains challenging since hydrophobic and hydrophilic moieties need to be combined in a single colloidal system. As a result, adjusting the micro−/nanogel amphiphilicity often changes the colloidal features too. To overcome these limitations, various strategies have been reported. The aim of this review is to give a brief overview of important synthetic tools, considering both advantages and disadvantages, thus critically evaluating their potential in different research fields

AuNP/MIL-88B-NH\u2082 nanocomposite for the valorization of nitroarene by green catalytic hydrogenation

Abstract: The efficiency of a catalytic process is assessed based on conversion, yield, and time effectiveness. However, these parameters are insufficient for evaluating environmentally sustainable research. As the world is urged to shift towards green catalysis, additional factors such as reaction media, raw material availability, sustainability, waste minimization and catalyst biosafety, need to be considered to accurately determine the efficacy and sustainability of the process. By combining the high porosity and versatility of metal organic frameworks (MOFs) and the activity of gold nanoparticles (AuNPs), efficient, cyclable and biosafe composite catalysts can be achieved. Thus, a composite based on AuNPs and the nanometric flexible porous iron(III) aminoterephthalate MIL-88B-NH2 was successfully synthesized and fully characterized. This nanocomposite was tested as catalyst in the reduction of nitroarenes, which were identified as anthropogenic water pollutants, reaching cyclable high conversion rates at short times for different nitroarenes. Both synthesis and catalytic reactions were performed using green conditions, and even further tested in a time-optimizing one-pot synthesis and catalysis experiment. The sustainability and environmental impact of the catalytic conditions were assessed by green metrics. Thus, this study provides an easily implementable synthesis, and efficient catalysis, while minimizing the environmental and health impact of the process

Magnetic Pd nanocatalyst Fe3O4Pd for C–C bond formation and hydrogenation reactions

Small core-shell Fe3O4@Pd superparamagnetic nanoparticles (MNPs) were obtained with good control in size and shape distribution by metal-complex thermal decomposition in organic media. The role of the stabilizer in the synthesis of MNPs was studied, employing oleylamine (OA), triphenylphosphine (TPP) and triphenylamine (TPA). The results revealed that, among the stabilizer investigated, the presence of oleylamine in the reaction media is crucial in order to obtain an uniform shell of Pd(0) in Fe3O4@Pd MNPs of 7 ± 1 nm. The synthesized core-shell MNPs were tested in Pd-catalyzed Heck-Mizoroki and Suzuki-Miyaura coupling reactions and p-chloronitrobenzene hydrogenation. High conversion, good reaction yields, and good TOF values were achieved in the three reaction systems with this nanocatalyst. The core-shell nanoparticle was easily recovered by a simple magnetic separation using a neodymium commercial magnet, which allowed performing up to four cycles of reuse.Fil: Biglione, Catalina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Cappelletti, Ariel Leonardo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Strumia, Miriam Cristina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Martín, Sandra Elizabeth. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Uberman, Paula Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentin

Design of Multifunctional Nanogels with Intelligent Behavior

The design of polymeric nanogels with novel properties (dimensional structure, mechanics, high water content and biocompatibility) continues to attract the attention of both scientific researchers and biomedical industries seeking new materials for application in areas such as tissue engineering, cell immobilization, separation of biomolecules or cells, biomedical implants, for use as diagnostic agents and in theranostics. The impressive progress in material and pharmaceutical sciences has given rise to the design of a broad range of nanogels of diverse size, architecture and surface properties. The nanoscopic scale of these nanocarriers permits systemic (intravenous) or local (mucosal) administration and facilitates their diffusion within the cell. Moreover, surface functionalization methodologies can impart to the nanocarriers the ability to control pharmacokinetic and bio-distribution.Interest in intelligent nanogels has grown in recent years owing to their capacity to regulate behavior in response to external physical, chemical and biological stimuli.The different methods of nanogel synthesis and the adequate structure/property ratio for intelligent behavior and novel applications will be described and discussed in this chapter, presenting the most significant progress achieved in recent years in the field of nanocarriers in biomedical applications.Fil: Rimondino, Guido Noé. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Biglione, Catalina. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Martinelli, Marisa. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Alvarez Igarzabal, Cecilia Ines. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Strumia, Miriam Cristina. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentin

Facile ultrasonication approach for the efficient synthesis of ethylene glycol-based thermoresponsive nanogels

The employment of nanogels (NGs) for drug delivery purposes has experienced a huge increase during thelast decades. Among the different NGs, those displaying stimuli-responsive properties are of special interest.In particular, NGs that are able to swell or shrink by the action of temperature are very promising materialsfor applications in the biomedical and biological fields. In this work we present the preparation ofthermoresponsive ethylene glycol-based NGs employing a simple and reliable ultrasonication approach.By this means, the reaction times could be shortened and the NGs formation could be performed evenat room temperature and in the presence of oxygen. The NGs have been characterized by differenttechniques and their cloud point could be tuned by changing the molar ratio between the monomers.Finally, the NGs were labelled with Rhodamine B and their cellular uptake and cytotoxicity have beenanalysed.Fil: Biglione, Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Sousa Herves, Anna . Freie Universität Berlin; AlemaniaFil: Menger, Martina . Freie Universität Berlin; AlemaniaFil: Wedepohl, Stefanie . Freie Universität Berlin; AlemaniaFil: Calderón, Marcelo . Freie Universität Berlin; AlemaniaFil: Strumia, Miriam Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentin

Poly(N-acryloylmorpholine) Nanogels as Promising Materials for Biomedical Applications: Low Protein Adhesion and High Colloidal Stability

Poly(N-acryloylmorpholine) (P(NAM))-based materials have been developed to prevent protein adhesion to surfaces due to their biocompatibility and protein-repellent properties. However, transferring the benefits of P(NAM) to nanoscale materials such as nanogels has not yet been studied. This can be attributed to the challenging colloidal synthesis of such particles with highly hydrophilic networks. To address this challenge, we have developed an inverse miniemulsion approach for free radical polymerization of NAM in dispersed nanodroplets. This strategy allows preparation of well-defined P(NAM) nanogels with a controllable size (250-350 nm). To impart additional functionality, our approach can easily be adapted to include ionic co-monomers and degradable cross-linkers. The resulting pH-responsive swelling and redox-triggered degradation profiles were demonstrated by dynamic light scattering measurements. To test the influence of such additional functionality on the protein-repellent properties, protein adsorption on the nanogels was assessed. For surface-immobilized nanogels, reduced unspecific binding of albumin was demonstrated for all nanogels via fluorescence microscopy. For nanogels in suspension, nanoparticle tracking analysis showed no increase in nanogel size upon incubation in serum and plasma, thus suggesting limited protein adsorption and colloidal high stability for over 2 months. Finally, cytotoxicity essays demonstrated the potential of these materials for bio-applications. Overall, these results suggest that biocompatibility and protein-repellent properties of P(NAM) can be transferred to nanogels and are maintained upon integration of additional chemical functionality. Thus, our synthetic strategy builds the foundation for utilizing such versatile colloidal materials in biomedical applications, e.g., as versatile drug delivery systems.Fil: Phuong Neumann Tran, Thi Mai. Freie Universität Berlin; AlemaniaFil: López Iglesias, Clara. Freie Universität Berlin; AlemaniaFil: Navarro, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Quaas, Elisa. Freie Universität Berlin; AlemaniaFil: Achazi, Katharina. Freie Universität Berlin; AlemaniaFil: Biglione, Catalina. Freie Universität Berlin; Alemania. Instituto Imdea Energia.; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Klinger, Daniel. Freie Universität Berlin; Alemani