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Tumor-targeted Chlorotoxin-coupled Nanoparticles for Nucleic Acid Delivery to G...

Costa, Pedro M.; Cardoso, Ana L.; Mendonça, Liliana S.; Serani, Angelo; Custódia, Carlos; Conceição, Mariana; Simões, Sérgio; Moreira, João N.

The present work aimed at the development and application of a lipid-based nanocarrier for targeted delivery of nucleic acids to glioblastoma (GBM). For this purpose, chlorotoxin (CTX), a peptide reported to bind selectively to glioma cells while showing no affinity for non-neoplastic cells, was covalently coupled to liposomes encapsulating antisense oligonucleotides (asOs) or small interfering RNAs (siRNAs). T...


Impact of anti-PLK1 siRNA-containing F3-targeted liposomes on the viability of ...

Gomes-da-Silva, Lígia C.; Ramalho, José S.; de Lima, M. C. P.; Simões, Sérgio; Moreira, João N.

We have previously described the development of novel sterically stabilized F3-targeted pH-sensitive liposomes, which exhibited the ability to target both cancer and endothelial cells. Herein, the therapeutic potential of those liposomes was assessed upon encapsulation of a siRNA against a well-validated molecular target, PLK1. Treatment of prostate cancer (PC3) and angiogenic endothelial (HMEC-1) cells with F3...


Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the...

Gomes-da-Silva, Lígia C.; Santos, Adriana O.; Bimbo, Luís M.; Moura, Vera; Ramalho, José S.; Lima, Maria C. Pedroso de; Simões, Sérgio; Moreira, João N.

The present work aimed at designing a lipid-based nanocarrier for siRNA delivery towards two cell sub-populations within breast tumors, the cancer and the endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the F3 peptide, which is specifically internalized by nucleolin overexpressed on both those sub-populations, was used as a targeting moiety. The developed F3-targeted stable nuc...


Metodologia de avaliação de aplicações para descrição de arquivo definitivo

Simões, Sérgio Manuel Duarte

Tese de mestrado, Ciências da Documentação e Informação Arquivística, Universidade de Lisboa, Faculdade de Letras, 2012 ; Este estudo centra-se na necessidade que os arquivistas têm de desenvolverem competências e metodologias que lhes permitam dialogar com os especialistas das Tecnologias da Informação quando se deparam com a avaliação de programas para descrição de arquivo definitivo. Para isso, é feita uma ...


Efficient Chemoenzymatic Synthesis, Cytotoxic Evaluation, and SAR of Epoxysterols

Carvalho, João F. S.; Silva, M. Manuel Cruz; Moreira, João N.; Simões, Sérgio; Melo, M. Luísa Sá e

A library of diastereomerically pure epoxysterols, prepared by combining chemical and enzymatic methodologies, was evaluated for cytotoxicity toward human cancer and noncancer cell lines. Unsaturated steroids were oxidized by magnesium bis(monoperoxyphthalate) hexahydrate in acetonitrile, and the resulting epimeric epoxides were enzymatically separated using Novozym 435 or lipase AY. Some of the synthesized epo...


African swine fever virus p10 protein exhibits nuclear import capacity and accu...

Nunes-Correia, Isabel; Rodríguez, Javier M.; Eulálio, Ana; Carvalho, Ana L.; Citovsky, Vitaly; Simões, Sérgio; Faro, Carlos; Salas, María L.

African swine fever virus (ASFV), a large enveloped DNA-containing virus, infects domestic and wild pigs, and multiplies in soft ticks, causing an economically relevant hemorrhagic disease. Evaluation of the nuclear import ability of ASFV p10 protein was the major purpose of the present work. Two approaches were used to determine if p10 protein is imported into the nucleus by an active process: a yeast-based nu...


Synthesis of amphiphilic sulfonamide halogenated porphyrins: MALDI-TOFMS charac...

Monteiro, Carlos J. P.; Pereira, Mariette M.; Pinto, Sara M. A.; Simões, Ana V. C.; Sá, Gonçalo F. F.; Arnaut, Luís G.; Formosinho, Sebastião J.

Porphyrins are key precursors for development of photosensitizers for photodynamic therapy. A new series of ortho-halogenated tetraarylporphyrins with sulfonamide substituents have been synthesized via chlorosulfonation reaction and characterized by MALDI-TOFMS. To predict their partition properties, log KOW of a selected range of the synthesized halogenated amphiphilic porphyrins is described. A significant ef...


S4 13 - PV cell penetrating peptide and cationic liposomes act synergistically...

Trabulo, Sara; Mano, Miguel; Faneca, Henrique; Cardoso, Ana Luísa; Duarte, Sónia; Henriques, Ana; Paiva, Artur; Gomes, Paula; Simões, Sérgio

Cell penetrating peptides have been successfully used to mediate the intracellular delivery of a wide variety of molecules of pharmacological interest. The main aim of the present work was to evaluate the potential of the S413-PV cell penetrating peptide to mediate the intracellular delivery of plasmid DNA, aiming at its use in gene therapy applications. The S413-PV cell penetrating peptide is a chimeric peptid...


Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease

Alves, Sandro; Régulier, Etienne; Nascimento-Ferreira, Isabel; Hassig, Raymonde; Dufour, Noelle; Koeppen, Arnulf; Carvalho, Ana Luísa; Simões, Sérgio

Machado-Joseph disease (MJD) is a fatal, dominant neurodegenerative disorder. MJD results from polyglutamine repeat expansion in the MJD-1 gene, conferring a toxic gain of function to the ataxin-3 protein. In this study, we aimed at overexpressing ataxin-3 in the rat brain using lentiviral vectors (LV), to generate an in vivo MJD genetic model and, to study the disorder in defined brain regions: substantia nigr...


Transferrin-Associated Lipoplexes as Gene Delivery Systems: Relevance of Mode o...

Penacho, Nuno; Filipe, Ana; Simões, Sérgio; Lima, Maria C. Pedroso de

Abstract The successful application of gene therapy depends highly on understanding the properties of gene carriers and their correlation with the ability to mediate transfection. An important parameter that has been described to improve transfection mediated by cationic liposomes involves association of ligands to cationic liposome–DNA complexes (lipoplexes). In this study, ternary complexes composed of 1,2-...


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    Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência Programa Operacional da Sociedade do Conhecimento União Europeia