Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity

The relaxivity displayed by Gd3+ chelates immobilized onto gold nanoparticles is the result of complex interplay between nanoparticle size, water exchange rate and chelate structure. In this work we study the effect of the length of -thioalkyl linkers, anchoring fast water exchanging Gd3+ chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd3+ chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM-1s-1 (30 MHz, 25 ºC) were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles is determined mainly by size. Small nanoparticles (HD= 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD= 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggests that functionalized gold nanoparticles hold great potential for further investigation as MRI Contrast Agents. This study contributes to understand the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd3+ complexes. It is a relevant contribution towards “design rules” for nanostructures functionalized with Gd3+ chelates as Contrast Agents for MRI and multimodal imaging.

An experimental investigation on nano-TiO2 and fly ash based high performance concrete

High performance concrete (HPC) offers several advantages over normal-strength concrete, namely, high mechanical strength and high durability. Therefore, HPC allows for concrete structures with less steel reinforcement and a longer service life, both of which are crucial issues in the eco-efficiency of construction materials. Nevertheless international publications on the field of concrete containing nanoparticles are scarce when compared to Portland cement concrete (around 1%) of the total international publications. HPC nanoparticle-based publications are even scarcer. This article presents the results of an experimental investigation on the mechanical properties and durability of HPC based on nano-TiO2 and fly ash. The durability performance was assessed by means of water absorption by immersion, water absorption by capillarity, ultrasonic pulse velocity, electric resistivity, chloride diffusion and resistance to sulphuric acid attack. The results show that the concretes containing an increased content of nano-TiO2 show decreased durability performance. The results also show that concrete with 1% nano-TiO2 and 30% fly ash as Portland cement replacement show a high mechanical strength (C55/C67) and a high durability. However, it should be noted that the cost of nano-TiO2 is responsible for a severe increase in the cost of concrete mixtures.

Preparação de suspensões aquosas de nanopartículas de carbono para deposição em superfícies

Dissertação de mestrado integrado em Engenharia de Materiais

Development of advanced cell/tissue culture systems, based on enhanced polymeric scaffolds and sophisticated bioreactors, for tissue engineering applications

Programa Doutoral em Engenharia Biomédica

Nanotechnological approaches using curcumin and Withania somnifera: neuroprotection and antimicrobial activities

Tese de Doutoramento em Biologia de Plantas

Development of folate-targeted liposomes for rheumatoid arthritis therapy

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Protein-based nanodevices for therapeutic applications

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

From software extensions to product lines of dataflow programs

Abstract Dataflow programs are widely used. Each program is a directed graph where nodes are computations and edges indicate the flow of data. In prior work, we reverse-engineered legacy dataflow programs by deriving their optimized implementations from a simple specification graph using graph transformations called refinements and optimizations. In MDE-speak, our derivations were PIM-to-PSM mappings. In this paper, we show how extensions complement refinements, optimizations, and PIM-to-PSM derivations to make the process of reverse engineering complex legacy dataflow programs tractable. We explain how optional functionality in transformations can be encoded, thereby enabling us to encode product lines of transformations as well as product lines of dataflow programs. We describe the implementation of extensions in the ReFlO tool and present two non-trivial case studies as evidence of our work’s generality

Resilience of concrete structures in the marine environment through microstructural innovation

Dissertação de mestrado integrado em Engenharia Civil

Development of polymeric nanoparticles containing neuroprotective compounds of Hypericum perforatum

Tese de Doutoramento em Biologia das Plantas - MAP BIOPLANT

Current approaches and future perspectives on strategies for the development of personalized tissue engineering therapies

Personalized tissue engineering and regenerative medicine (TERM) therapies propose patient-oriented effective solutions, considering individual needs. Cell-based therapies, for example, may benefit from cell sources that enable easier autologous set-ups or from recent developments on IPS cells technologies towards effective personalized therapeutics. Furthermore, the customization of scaffold materials to perfectly fit a patientâ s tissue defect through rapid prototyping technologies, also known as 3D printing, is now a reality. Nevertheless, the timing to expand cells or to obtain functional in vitrotissue substitutes prior to implantation prevents advancements towards routine use upon patient´s needs. Thus, personalized therapies also anticipate the importance of creating off-the-shelf solutions to enable immediately available tissue engineered products. This paper reviews the main recent developments and future challenges to enable personalized TERM approaches and to bring these technologies closer to clinical applications.

Synthetic biology approaches to engineer new pathways for the production of plant secondary metabolites

Secondary metabolites from plants are important sources of high-value chemicals, many of them being pharmacologically active. These metabolites are commonly isolated through inefficient extractions from natural biological sources and are often difficult to synthesize chemically. Therefore, their production using engineered organisms has lately attracted an increased attention. Curcuminoids, an example of such metabolites, are produced in Curcuma longa and exhibit anti-cancer and anti-inflammatory activities. Herein we report the construction of an artificial biosynthetic pathway for the curcuminoids production in Escherichia coli. Different 4-coumaroyl-CoA ligases (4CL) and polyketide synthases (diketide-CoA synthase (DCS), curcumin synthase (CURS) and curcuminoid synthase) were tested. The highest curcumin production (70 mg/L) was obtained by feeding ferulic acid and with the Arabidopsis thaliana 4CL1 and C. longa DCS and CURS enzymes. Other curcuminoids (bisdemethoxy- and demethoxycurcumin) were also produced by feeding coumaric acid or a mixture of coumaric and ferulic acids, respectively. Curcuminoids, including curcumin, were also produced from tyrosine through the caffeic acid pathway. To produce caffeic acid, tyrosine ammonia lyase and 4-coumarate 3-hydroxylase were used. Caffeoyl-CoA O-methyltransferase was used to convert caffeoyl-CoA to feruloyl-CoA. This pathway represents an improvement of the curcuminoids heterologous production. The construction of this pathway in another model organism is being considered, as well as the introduction of alternative enzymes.

Superhydrophobic surfaces as a tool for the fabrication of hierarchical spherical polymeric carriers

Hierarchical polymeric carriers with high encapsulation efficiencies are fabricated via a biocompatible strategy developed using superhydrophobic (SH) surfaces. The carries are obtained by the incorporation of cell/BSA-loaded dextran-methacrylate (DEXT-MA) microparticles into alginate (ALG) macroscopic beads. Engineered devices like these are expected to boost the development of innovative and customizable systems for biomedical and biotechnological purposes.

Highly robust hydrogels via a fast, simple and cytocompatible dual crosslinking-based process

A highly robust hydrogel device made from a single biopolymer formulation is reported. Owing to the presence of covalent and non-covalent crosslinks, these engineered systems were able to (i) sustain a compressive strength of ca. 20 MPa, (ii) quickly recover upon unloading, and (iii) encapsulate cells with high viability rates.

In vivo imaging of glycol chitosan-based nanogel biodistribution

The preclinical development of nanomedicines raises several challenges and requires a comprehensive characterization. Among them is the evaluation of the biodistribution following systemic administration. In previous work, the biocompatibility and in vitro targeting ability of a glycol chitosan (GC) based nanogel have been validated. In the present study, its biodistribution in the mice is assessed, using near-infrared (NIR) fluorescence imaging as a tool to track the nanogel over time, after intravenous administration. Rapid whole body biodistribution of both Cy5.5 labeled GC nanogel and free polymer is found at early times. It remains widespreadly distributed in the body at least up to 6 h postinjection and its concentration then decreases drastically after 24 h. Nanogel blood circulation half-life lies around 2 h with the free linear GC polymer presenting lower blood clearance rate. After 24 h, the blood NIR fluorescence intensity associated with both samples decreases to insignificant values. NIR imaging of the organs shows that the nanogel had a body clearance time of 48 h, because at this time point a weak signal of NIR fluorescence is observed only in the kidneys. Hereupon it can be concluded that the engineered GC nanogel has a fairly long blood circulation time, suitable for biomedical applications, namely, drug delivery, simultaneously allowing efficient and quick body clearance.