Design and Study of Multifunctional Systems Based on Magnetic Nanoparticles for Biomedical Applications

Nanomedicine is a new field employing nanotechnology tools for biomedical applications. Nanomaterials feature sizes between 1 and 100 hundred nanometers, and therefore they fill the gap between single molecules and bulk materials. They open the possibility to access biological processes on the same size scale. Nanoparticles have shown great potential to achieve the goal of personalized medicine due to the possibilities to modify their surface with proteins, targeting molecules, or imaging probes. Particularly, iron oxide nanoparticles show promising properties for successful application in biomedicine due to their low-cost production, high biocompatibility, and great magnetic response. Strategies for the functionalization of inorganic cores have been developed over the past years, and efforts have been devoted to engineering nanoparticles with multifunctional ligands on the surface to enable active tumor targeting, detection over different imaging modalities, and stimulus-driven cargo release. During this Ph.D. thesis, three main aspects of iron oxide nanoparticles have been evaluated. First, the stability of nanoparticles has been addressed in biological fluids. Second, the uptake of nanoparticles by stem cells for cell tracking applications was studied with nanoparticles of different sizes and bearing different organic coatings. Third, new possibilities of chemical functionalization of naked iron oxide nanoparticles by orthogonal processes have been explored, in order to achieve high yields, simplicity and high reproducibility

A dendrimer–hydrophobic interaction synergy improves the stability of polyion complex micelles

This work was financially supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) (CTQ2015‐ 69021‐R), the Consellería de Cultura, Educación e Ordenación Universitaria (GRC2014/040 and Centro Singular de Investigación de Galicia Accreditation 2016‐2019, ED431G/09), and the European Regional Development Fund (ERDF). M.F.‐V. thanks the Spanish Government for a FPU FellowshipPolyion complex (PIC) micelles incorporating PEG-dendritic copolymers display an unprecedented stability towards ionic strength that is amplified via hydrophobic interactions. The tridimensional orientation of peripheral hydrophobic linkers between charged groups and the globular/rigid dendritic scaffold maximizes this stabilization compared to PIC micelles from linear polymers. As a result, micelles stable at concentrations higher than 3 M NaCl are obtained, which represents the highest saline concentration attained with PIC micelles. Advantages of this stabilizing dendritic effect have been taken for the design of a robust, pH-sensitive micelle for the controlled intracellular release of the anticancer drug doxorubicin. This micelle displays a slightly higher toxicity, and distinctive mechanisms of cell uptake and intracellular trafficking relative to the free drug. The preparation of mixed PIC micelles by combining differently functionalized PEG-dendritic block copolymers has allowed the fine-tuning of their stability, paving the way towards the facile modulation of properties like biodegradability, drug loading, or the response to external stimuliS

A post-synthetic modification strategy for the synthesis of pyrene-fused azaacene covalent organic frameworks

Post-synthetic modification strategy is presented to extend the π-system of covalent organic framework (COF) backbone giving access to boronic ester based pyrene-fused azaacene COFs. Optimized catalyst-free reaction conditions yield COFs post-synthetically modified with up to 33% conversion and corresponding intriguing optical properties. The presented chemistry is expected to find application in post-synthetic tailoring of the optical properties of COFs.S.P.S.F. acknowledges the FCT − Fundação para a Ciência e Tecnologia for the Ph.D. scholarship SFRH/BD/131791/2017. This work received funding from the COFforH2 project (UTA-EXPL/NPN/0055/2019) through the Portuguese Foundation for Science and Technology funds under UT Austin Portugal, Charm project (PTDC/QUI-OUT/2095/2021) through the Portuguese Foundation for Science and Technology funds, The Excellence Clusters ‘Nanosystems Initiative Munich (NIM)’, and from the Free State of Bavaria through the Research Network ‘Solar Technologies go Hybrid’.Peer reviewe

A dendrimer-hydrophobic interaction synergy improves the stability of polyion complex micelles

© The Royal Society of Chemistry. Polyion complex (PIC) micelles incorporating PEG-dendritic copolymers display an unprecedented stability towards ionic strength that is amplified via hydrophobic interactions. The tridimensional orientation of peripheral hydrophobic linkers between charged groups and the globular/rigid dendritic scaffold maximizes this stabilization compared to PIC micelles from linear polymers. As a result, micelles stable at concentrations higher than 3 M NaCl are obtained, which represents the highest saline concentration attained with PIC micelles. Advantages of this stabilizing dendritic effect have been taken for the design of a robust, pH-sensitive micelle for the controlled intracellular release of the anticancer drug doxorubicin. This micelle displays a slightly higher toxicity, and distinctive mechanisms of cell uptake and intracellular trafficking relative to the free drug. The preparation of mixed PIC micelles by combining differently functionalized PEG-dendritic block copolymers has allowed the fine-tuning of their stability, paving the way towards the facile modulation of properties like biodegradability, drug loading, or the response to external stimuli.status: publishe

Straightforward phase-transfer route to colloidal iron oxide nanoparticles for protein immobilization

© The Royal Society of Chemistry 2015. We report for the first time the effective transfer of hydrophobic oleate-capped iron oxide nanoparticles to an aqueous phase upon treatment with a base bath cleaning solution. We discuss the mechanism of the phase transfer, which involves the elimination of the organic capping agent followed by ionic stabilization of the nanoparticles due to negatively charged Fe-O- surface species. The resultant superparamagnetic aqueous nanocolloid shows excellent protein immobilization capability.status: publishe

Design and Synthesis of Highly Active Al-Ni-P Foam Electrode for Hydrogen Evolution Reaction

© 2015 American Chemical Society. An effective method to boost the electrocatalytic activity of nickel phosphides in H2 evolution reaction is reported. The method took advantage of density functional theory calculations that allowed the design of a highly active material based on the combination of d-metal with p-metal within a phosphide structure. Furthermore, the principle is proven experimentally through successful synthesis of self-supported ternary Al-Ni-P foam electrocatalyst by alloying of Ni and Al followed by the gas transport phosphorization reaction. As a cathode for H2 evolution reaction in acidic electrolyte, Al-Ni-P significantly outperforms pure Ni-P, and it has an exchange current density of 0.6 mA/cm2 and a Tafel slope of 65 mV/decade.status: publishe

Influence of of the separation procedure on the properties of magnetic nanoparticles: Gaining in vitro stability and T-1-T-2 magnetic resonance imaging performance

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) coated with polyacrylic acid (PAA) were synthesized by a hydrothermal method in gram-scale quantity and extensively characterized. Only the nanoparticles subjected to an additional centrifugation step showed narrow size distribution, high polymeric coverage, and ideal superparamagnetism. In addition to improved physico-chemical properties, these nanoparticles feature high stability in vitro as well as dual T1-T2 performance as contrast agents (CAs) for magnetic resonance imaging (MRI), highlighting the importance of the additional separation step in obtaining material with the desired properties.status: publishe

A supramolecular strategy based on molecular dipole moments for high-quality covalent organic frameworks

\u3cp\u3eA supramolecular strategy based on strong molecular dipole moments is presented to gain access to covalent organic framework structures with high crystallinity and porosity. Antiparallel alignment of the molecules within the pore walls is proposed to lead to reinforced columnar stacking, thus affording a high-quality material. As a proof of principle, a novel pyrene dione building block was prepared and reacted with hexahydroxytriphenylene to form a boronic ester-linked covalent organic framework. We anticipate the strategy presented herein to be valuable for producing highly defined COF structures.\u3c/p\u3

A supramolecular strategy based on molecular dipole moments for high-quality covalent organic frameworks

A supramolecular strategy based on strongmolecular dipole moments is presented to gain access to covalent organic framework structures with high crystallinity and porosity. Antiparallel alignment of the molecules within the pore walls is proposed to lead to reinforced columnar stacking, thus affording a high-quality material. As a proof of principle, a novel pyrene dione building block was prepared and reacted with hexahydroxytriphenylene to form a boronic ester-linked covalent organic framework. We anticipate the strategy presented herein to be valuable for producing highly defined COF structures

Magnetite Nanoparticles for Stem Cell Labeling with High Efficiency and Long-Term in Vivo Tracking

Superparamagnetic iron oxide nanoparticles (SPIO-PAA), ultrasmall iron oxide nanoparticles (USPIO-PAA), and glucosamine-modified iron oxide nanoparticles (USPIO-PAA-GlcN) were studied as mesenchymal stem cell (MSCs) labels for cell tracking applications by magnetic resonance imaging (MRI). Pronounced differences were found in the labeling performance of the three samples in terms of cellular dose and labeling efficiency. In combination with polylysine, SPIO-PAA showed nonhomogeneous cell internalization, while for USPIO-PAA no uptake was found. On the contrary, USPIO-PAA-GlcN featured high cellular uptake and biocompatibility, and sensitive detection in both in vitro and in vivo experiments was found by MRI, showing that glucosamine functionalization can be an efficient strategy to increase cell uptake of ultrasmall iron oxide nanoparticles by MSCs.status: publishe