Projects In-Course

1  PROJECT : Desenvolvimento de novos vectores nano-poliplexos como agentes de imagem e libertação contra o cancro de mama triple negativo”, (PTDC/QEQ-MED/2118/2014).

FINANCIAL ENTITY: Fundação para a Ciencia e a Tecnologia, FCT MEC

FUNDING PERIOD:  From 05, 2016 – 04, 2019 (36 months)

INSTITUTIONS: University NOVA of Lisbon (FCT); University of Tras os Montes e Alto Douro (UTAD) and Proteomass Scientific Society (Caparica)

PI: Prof. Dr. Carlos Lodeiro (FCT-UNL).

Other researchers: Jose Luis Capelo; Hugo Miguel Santos; Elisabete Oliveira; Javier Fdez Lodeiro; Adrián Fdez Lodeiro; Cristina Nuñez; Gilberto Igrejas; Eduardo Araujo.

Funding: 87.511 euros

Abstract:

Despite a significant progress in early diagnosis and treatment, resistance to conventional chemotherapeutics continuously poses a tremendous challenge to effective triple breast cancer therapy.

The present project proposes the development of novel nanocarrier systems to deliver miR34a and different drugs ((D) = Docetaxel (DCT), Doxorubicin (DOX), Paclitaxel (PXL) and Nintedanib (NTB)) in human triple negative breast cancer cells (MDAMB231) to inhibit both, their growth and migration.

For this aim, novel non viral  nanopolyplex vectors containing oligosaccharide fragments of hyaluronic acid (oHA) with high affinity for the surface receptor CD44 overexpressed in human triple negative breast cancer cells (MDAMB231) will be designed. It will be the first time that oHA will be used to the creation of non viral gene delivery systems. It is expected that this strategy could improve the encapusalting capacity of the nanopolyplexes and their in vitro and in vivo antitumor activity.

This proposed research will cover a vast range of interdisciplinary research, starting from the design and synthesis of novel nanopolyplexes systems, structural and physical characterization of the synthesized materials, encapsulation of gene and drugs and study of their properties for gene and drug delivery in a triple breast cancer model.

2  PROJECT : NOVA_Health Projet Pilot 02 “ Biomarkers of Rheumatic Inflammatory diseases diagnosis”

FINANCIAL ENTITY: iNOVA Health, University NOVA of Lisbon, Rectorate

FUNDING PERIOD:  From 09, 2014 – 18 months

INSTITUTIONS: University NOVA of Lisbon (FCT); University NOVA of Lisbon (FCM) and Proteomass Scientific Society (Caparica)

Principal Researcher: Prof. Dr. Jose Luis Capelo (FCT-UNL) / Prof. Fernando Pimentel (CEDOC-FCM-UNL)

Other researchers: Carlos Lodeiro, Hugo M. Santos, Susana Jorge

Funding: 12.000 euros

Abstract:

Currently, Ankylosing spondylitis (AS), Systemic lupus erythematosus (SLE) and Rheumatoid arthritis (RA) are three diseases related to ageing in which an early diagnosis is challenging, as the clinic is similar between them and easily confused with others entities such as infections or cancers. This problem makes difficult a correct diagnostic, and consequently difficult a therapeutic approach at the early stages of such diseases. The current markers, Rheumatoid factor, anti-CCP, ANA, Anti-DNA, Anti-Sm are frequently negative in earlier stages or may reflect false positives; in other way HLA B27 gene has low specificity for AS. So in clinical practice new biomarkers may be helpful for patients and clinicians.

This project aims to establish a quick method to stratify patients of the three diseases- AS, SLE, RA, hopefully since early stages (second part of the project). The method is based on a analytical methodology already proven with success in stratifying patients with osteoarthritis , that was developed by our Team  and in the inputs regarding classification of  patients provided by the Prof. Pimentel team.

PROJECT : NOVA_Health Projet Pilot 01 “ Discovery of Biomarkers for Bladder Carcinoma Diagnosis.”

FINANCIAL ENTITY: iNOVA Health, University NOVA of Lisbon, Rectorate

FUNDING PERIOD:  From 09, 2014 – 18 months

INSTITUTIONS: University NOVA of Lisbon (FCT); University NOVA of Lisbon (FCM) and Proteomass Scientific Society (Caparica)

Principal Researcher: Dr. Hugo Miguel Santos (UNL) / Prof. Paula Videira (CEDOC-UNL)

Other researchers: Carlos Lodeiro, Jose Luis Capelo, Eduardo Araujo

Funding: 12.000 euros

Abstract:

Bladder carcinoma diagnostic lacks in accuracy. Furthermore, recurrence of this cancer is high, which makes the five-year survival ratio for this disease one of the worst of all carcinomas.  In addition, up to date there is no effective biomarkers that can allow for monitoring therapy for this disease.

 This project aims to establish a quick method to stratify bladder patients in order to perform a better diagnostic and monitoring of therapeutics. The method is based on an analytical methodology already used with success in stratifying patients with osteoarthritis, that was developed by our Team. The rational of this study springs from previous investigations on bladder cancer biomarkers from Prof. Videira´s team and the inputs regarding classification of patients provided by the clinicians. 

4 PROJECT :  401797/2013-9 “Novel fluorescence probes containing selenium and/or tellurium atoms for the study of reactive oxygen species (ROS) supported in metallic nanoparticles: Towards new biomedical nano-tools. (ROS@SeTeMNP)

FINANCIAL ENTITY: CNPQ- Science without Borders, Invited Special Researcher

FUNDING PERIOD:  From January 01, 2014 – December 2017.

INSTITUTIONS: University NOVA of Lisbon (FCT); University of Sao Paulo, Institute of Chemistry (USP) 

Principal Researcher: Prof. Alcindo A dos Santos (USP Brasil) , Prof. Carlos Lodeiro (FCT-Portugal). 

Other researchers: Jose Luis Capelo; Hugo Miguel Santos; Elisabete Oliveira; Javier Fdez Lodeiro; Augusto Cesar Gonçalves, Antonio Soares Paulino.

Funding:  R$ 130,000,00 + 96,000,00 ; 3 Postdoctoral grants for 6 month each; 3 PhD grants for a year each.

Abstract:
Fluorescent probes that have excitation wavelengths in the far-red to near-infrared (NIR) (>600 nm) region are attractive for biological applications because of minimum photodamage to biological samples, deep tissue penetration, and minimum interference from the background autofluorescence of biomolecules in the living systems. Currently significant efforts are being made towards the use of NIR probes for bioanalytical applications. Unfortunately, few fluorophores show sufficient fluorescence quantum yields in the NIR region, especially in aqueous surroundings.

Therefore, the development of new far-red to NIR fluorophores with high fluorescence quantum yields and tolerance to photobleaching, and whose fluorescence can be easily controlled, is highly attractive.

On the other hand, it is well known that living cells are exposed to various stresses, such as reactive oxygen species (ROS), UV light, and metal ions.  Among them, ROS especially play important roles in a variety of biological and pathological systems. Overproduction of ROS is associated with many diseases, including acute and chronic inflammation, cancer, cardiovascular disease, and neurodegenerative disorders.


Generally, living cells are protected from oxidative stresses by intracellular redox systems, such as glutathione (GSH) and thioredoxin. Although reported fluorescence ROS probes are very useful for sensing ROS, the generated fluorescent products are generally irreversibly fluorescent.


For this purpose, reversible ROS probes, which detect ROS (oxidative environment) and also GSH (reductive environment) are required. Development of such reversible fluorescence probes for ROS is currently one of the most challenging topics in the field.


Having in mind this idea and with the knowledge that compounds with various oxidation states, such as those containing chalcogen atoms, sulfur (S) and selenium (Se), might also be applicable to the design of novel reversible ROS probes, we propose the design of novel near-infrared fluorescence probes for reactive oxygen species (ROS) based on X-rhodamine, X-fluorescein and X-coumarin (X= Te, S, Se)

5 PROJECT :Application of metallomics and proteomics strategies in the identification of possible biomarkers to bipolar disorder (88881.062204/2014-01) 

FINANCIAL ENTITY:  CAPES – Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior. Invited Special Researcher (Brazil)

Principal investigator: Prof. Marco Aurelio Zezzi Arruda (IQ/Unicamp-Brazil), Prof. Jose Luis Capelo (UNL-Portugal)

FUNDING PERIOD: July, 1st, 2014 – August, 30th, 2017

INSTITUTIONS: University NOVA of Lisbon (FCT); University of Campinas, Institute of Chemistry (UniCAMP) 

Other researchers:  Miguel Santos; Jemmyson Romario.
Funding: R$ 140.600,00; 1 Visiting professor grant; 2 postdoctoral grants (12 months each); 1 sandwich doctoral (12 months)

Abstract
This research project aims to the develop of new proteomics and comparative metallomics analysis applied to healthy and BIPOLAR disorder (TAB) patients using  blood serum samples. The study are based on the application of Two-dimensional electrophoresis in polyacrylamide gel electrophoresis (2DPAGE), mass spectrometry (MALDI-QTOF MS and ESI-QTOF MS) and ICP-MS techniques and PAGE-LA-ICP-MS.

 The subjects compose groups with mental disorders recruited from the Psychiatric Service of UNICAMP University Hospital. 

6 PROJECT : Sythesis and Characerization of New Fluorescent Nanomaterials for Biomedical and Environmental Applications. (APQ-00360-14) 

FINANCIAL ENTITY:  FAPEMIG – Fundação para o Apoio a Pesquisa do Estado de Minas Gerais (Brazil)

Principal investigator: Prof. Viviane Pilla (Uberlandia-Brazil) 

FUNDING PERIOD: March, 1st, 2015 – April, 1st, 2017

INSTITUTIONS: University NOVA of Lisbon (FCT); University of Uberlândia, Institute of Physics (UniCAMP) 

Other researchers:  Djalmir Nestor Messias, Acacio Andrade, Carlos Lodeiro, Elisabete Oliveira, Jose Luis Capelo, Hugo M. Santos.

Abstract:

This research project consists in the development of new sustainable synthetic routes of new functionalized nanomaterials with potential application for environmental analysis and biomedical tools. Spectroscopic characterizations, morphological and thermal optics will be performed in the new fluorescent nanomaterials derived from silver, gold and silica nanoparticles, as well as in quantum dots (or quantum dots QDs) functionalized with emissive fluorophores in the red region. Various techniques such as fluorescence, absorption, transmittance electron microscopy, mass spectrometry, scanning electron microscope and lifetime will be used for spectroscopic, optical and morphological characterization of the new nanoparticles. In thermo-optical characterizations apply the thermal lens technique, aiming the characterization of the thermal parameters, such as thermal diffusivity and the variation of refractive index with temperature, and the fluorescence quantum efficiency of the new fluorescent nanoparticles.

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