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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...


On the use of dexamethasone-loaded liposomes to induce the osteogenic different...

Monteiro, Nelson; Martins, Albino; Ribeiro, Diana Margarida da Costa; Faria, Susana, 1972-; Fonseca, Nuno A.; Moreira, João N.; Reis, R. L.

Stem cells have received considerable attention by the scientific community because of their potential for tissue engineering and regenerative medicine. The most frequently used method to promote their differentiation is supplementation of the in vitro culture medium with growth/differentiation factors (GDFs). The limitations of that strategy caused by the short half-life of GDFs limit its efficacy in vivo and ...


Immobilization of bioactive factor-loaded liposomes at the surface of electrosp...

Monteiro, Nelson; Martins, Albino; Pires, R. A.; Faria, Susana, 1972-; Fonseca, Nuno A.; Moreira, João N.; Reis, R. L.; Neves, N. M.

Publicado em "Journal of Tissue Engineering and Regenerative Medicine", vol. 7, supp. 1 (2013) ; The ability to manipulate and control the surface properties is of crucial importance in the designing of scaffolds for Tissue Engineering (TE) and Regenerative Medicine. Electrospun nanofibers (NFM), due to their morphology and fibrous structure have received much attention as potential biomedical devices, TE scaf...


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...


Induction of human mesenchymal stem cells osteogenesis by bioactive agent-relea...

Monteiro, Nelson; Martins, Albino; Ribeiro, Diana Margarida da Costa; Faria, Susana, 1972-; Fonseca, Nuno A.; Moreira, João N.; Reis, R. L.

Stem cell therapy is a rapidly evolving area of research in regenerative medicine. Mesenchymal stem cells (MSCs) have received considerable attention by the scientific community because of their potential of expansion and the ability to differentiate into various mesodermal tissues. Liposomes are well-established non-viral carrier systems, presenting significant advantages over other nanoparticle-based drug del...


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...


Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia ...

Fonseca, Cristina; Moreira, João N.; Ciudad, Carlos J.; Pedroso de Lima, Maria C.; Simões, Sérgio

The main aim of this work was to develop novel targeted sterically stabilised pH-sensitive liposomes tailored to promote efficient intracellular delivery of therapeutic molecules into human T-leukaemia cells. Our results indicate that the targeting moiety (thiolated transferrin) was successfully coupled to the distal reactive maleimide terminus of poly(ethylene glycol)-phospholipid conjugates incorporated in th...


Use of the Post-Insertion Technique to Insert Peptide Ligands into Pre-Formed S...

Moreira, João N.; Ishida, Tatsuhiro; Gaspar, Rogério; Allen, Theresa M.

Purpose: Simple methods for the large-scale manufacture of ligand-targeted liposomes will be needed if clinical trials are to proceed. We tested a recently developed technology for inserting peptide ligands into preformed Stealth liposomes. Antagonist G-targeted liposomes (PLG) were prepared and loaded with doxorubicin and their cellular association and cytotoxicity were evaluated using the human small cell lun...


Targeting Stealth liposomes in a murine model of human small cell lung cancer

Moreira, João N.; Gaspar, Rogério; Allen, Theresa M.

Tumor accumulation and therapeutic activity of Stealth liposomes loaded with doxorubicin (DXR) were examined in Balb/c nude mice xenografts inoculated subcutaneously with the human small cell lung cancer (SCLC) cell line, H69. Mice were treated with non-targeted liposomes (SL) or liposomes targeted with antagonist G coupled to the liposome surface (SLG). SLG showed 30-44-fold higher binding to H69 cells harvest...


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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