Centre for Nuclear Sciences and Technologies

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Pt-Fe ferrocenyl compounds with hydroxyquinoline ligands show selective cytotoxicity on highly proliferative cells

Publication . Rivas, Feriannys; Medeiros, Andrea; Comini, Marcelo; Suescun, Leopoldo; Rodríguez Arce, Esteban; Martins, Marta; Pinheiro, Teresa; Marques, Fernanda; Gambino, Dinorah

Searching for a more effective chemotherapy for the treatment of Human African trypanosomiasis, the disease caused by the parasite Trypanosoma brucei, and cancer, in the current work five new [PtII(L)(dppf)](PF6) compounds, with HL = 8-hydroxyquinoline derivatives and dppf = 1,1'-bis(diphenylphosphino)ferrocene, were synthesized and fully characterized. Crystal structures of three compounds were solved by XRD. The compounds displayed fairly good activity against bloodstream T. brucei, with IC50 values in the submicromolar range (IC50: 0.14-0.93 μM), and good selectivity towards the pathogen (SI: 11 - 48) with respect to mammalian macrophages (cell line J774). Coordination to the {Pt-dppf} moiety led, in most cases, to an enhancement of the activity in respect to the bioactive ligands (11 to 41 fold). Cytotoxicity was assessed against wildtype (A2780) and cisplatin-resistance (A2780cisR) ovarian cancer cell lines. Four [PtII(L)(dppf)](PF6) compounds were more active (IC50: 1.2-4.4 μM) than cisplatin (IC50: 26.0 μM) on A2780 cells and showed far superior activity than the reference drug against A2780cisR cells. Platinum levels in A2780 cells showed poor correlation between cellular uptake and the cytotoxic activity. All the complexes interacted with DNA and the most active ones induced reactive oxygen species (ROS) formation which suggested that the mechanism of action for these complexes may be mediated by oxidative stress and interaction with DNA that could act as a potential molecular target for this type of complexes. Some complexes of this series could be considered new hits for the development of prospective agents against trypanosomatid parasites and ovarian cancer.

2019Journal article

Restricted access

Os metais das necrópoles de cistas de Casas Velhas (Melides) e da Provença (Sines). O encontro de antigas e novas tecnologias no Bronze Pleno do Sudoeste

Publication . Valério, Pedro; Araújo, Maria de Fátima; Soares, António M. Monge; Soares, Joaquina; Silva, Carlos Tavares da

O estudo consiste na caracterização do espólio metálico das necrópoles de cistas de Casa Velhas e da Provença. Os artefactos de base cobre são compostos por cobre arsenical (2,03-5,64% As), exceptuando-se um “anzol” em bronze, liga que constitui uma das inovações do Bronze Pleno do Sudoeste, tal como a prata, aqui utilizada em ornamentos: anel (99,7% Ag) e bracelete (94,5% Ag; 5,41% Cu). Uma conta em ouro (12,6% Ag; <0,04% Cu) terá sido manufacturada em ouro de aluvião, tal como a maioria dos ouros pré-históricos. Por último, integram-se os resultados na metalurgia no sul de Portugal durante o II milénio a.C.

2019Journal article

Open access

Novel peptides derived from dengue virus capsid protein translocate reversibly the blood−brain barrier through a receptor-free mechanism

Publication . Neves, Vera; Silva, Frederico Aires da; Morais, Maurício; Gano, Lurdes; Ribeiro, Elisabete; Pinto, Antónia; Aguiar, Sandra; Gaspar, Diana; Fernandes, Célia; Correia, João D. G.; Castanho, Miguel A. R. B.

The delivery of therapeutic molecules to the central nervous system is hampered by poor delivery across the blood-brain barrier (BBB). Several strategies have been proposed to enhance transport into the brain, including invasive techniques and receptor-mediated transport (RMT). Both approaches have several drawbacks, such as BBB disruption, receptor saturation, and off-target effects, raising safety issues. Herein, we show that specific domains of Dengue virus type 2 capsid protein (DEN2C) can be used as trans-BBB peptide vectors. Their mechanism of translocation is receptor-independent and consistent with adsorptive-mediated transport (AMT). One peptide in particular, named PepH3, reaches equilibrium distribution concentrations across the BBB in less than 24 h in a cellular in vitro assay. Importantly, in vivo biodistribution data with radiolabeled peptide derivatives show high brain penetration. In addition, there is fast clearance from the brain and high levels of excretion, showing that PepH3 is a very good candidate to be used as a peptide shuttle taking cargo in and out of the brain.

2017Journal article

Restricted access

3D-printed platform multi-loaded with bioactive, magnetic nanoparticles and an antibiotic for re-growing bone tissue

Publication . Saraiva, Ana S.; Ribeiro, Isabel A. C.; Fernandes, Maria H.; Cerdeira, Ana Cláudia; Vieira, Bruno J.C.; Waerenborgh, João Carlos; Pereira, Laura C.J.; Cláudio, Ricardo; Carmezim, Maria João; Gomes, Pedro; Gonçalves, Lídia; Santos, Catarina F.; Bettencourt, Ana

Polymeric platforms obtained by three-dimensional (3D) printing are becoming increasingly important as multifunctional therapeutic systems for bone treatment applications. In particularly, researchers aim to control bacterial biofilm on these 3D-platforms and enhance re-growing bone tissue, at the same time. This study aimed to fabricate a 3D-printed polylactic acid platform loaded with hydroxyapatite (HA), iron oxide nanoparticles (IONPs) and an antibiotic (minocycline) with tuneable properties and multistimuli response. IONPs were produced by a facile chemical co-precipitation method showing an average diameter between 11 and 15 nm and a superparamagnetic behaviour which was preserved when loaded into the 3D-platforms. The presence of two types of nanoparticles (IONPs and HA) modify the nanomorphological/nanotopographical feature of the 3D-platforms justifying their adequate bioactivity profile and in vitro cellular effects on immortalized and primary osteoblasts, including cytocompatibility and increased osteogenesis-related gene expression (RUNX2, BGLAP and SPP1). Disk diffusion assays and SEM analysis confirmed the effect of the 3D-platforms loaded with minocycline against Staphylococcus aureus. Altogether results showed that fabricated 3D-platforms combined the exact therapeutic antibiofilm dose of the antibiotic against S. aureus, with the enhanced osteogenic stimulation of the HA and IONPs nanoparticles which is a disruptive approach for bone targeting applications.

2021-01Journal article

Open access