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Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple...

Ferreira, Débora Carina Gonçalves Abreu; Pereira, Cátia Sofia Santos; Costa, Marta; Afonso, Julieta Alexandra Pereira; Yang, Sujuan; Hensel, Janine

Available online 28 September 2023; Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines ...


Nucleolin Overexpression Predicts Patient Prognosis While Providing a Framework...

Fernandes, Ângela Valério; Fonseca, Nuno A.; Gonçalves, Nélio; Cruz, Ana F.; Pereira, Marta I.; Gregório, Ana C.; Moura, Vera; Ladeirinha, Ana F.

Notwithstanding the advances in the treatment of lung cancer with immune checkpoint inhibitors, the high percentage of non-responders supports the development of novel anticancer treatments. Herein, the expression of the onco-target nucleolin in patient-derived pulmonary carcinomas was characterized, along with the assessment of its potential as a therapeutic target. The clinical prognostic value of nucleolin f...


Exosome-mediated MEK1 silencing is a promising approach against triple negative...

Ferreira, Débora; Cátia S. Pereira; Costa, Marta; Afonso, Julieta; Longatto, Adhemar; Baltazar, Fátima; Kalluri, Raghu; Moreira, João N.

[Excerpt] Introduction: Breast cancer is a major public health problem worldwide being the most diagnosed cancer in women [1] . Triple negative breast cancer (TNBC) represents 10-20% of all breast cancers and is characterized by the absence of hormone receptors (progesterone and estrogen) and lack of expression of epidermal growth factor receptor 2. Furthermore, it is also described to have poor prognosis due t...


GMP-grade nanoparticle targeted to nucleolin downregulates tumor molecular sign...

Fonseca, Nuno A.; Gregório, Ana C.; Mendes, Vera M.; Lopes, Rui; Abreu, Teresa; Gonçalves, Nélio; Manadas, Bruno; Lacerda, Manuela; Figueiredo, Paulo

Patients with breast or ovarian cancer have not benefited from improved efficacy with pegylated liposomal doxorubicin relative to free drug, likely due to the limited extent of the enhanced permeability and retention (EPR) effect, further compromising drug bioavailability in the tumor. Herein it is hypothesized that targeting nucleolin overexpressed in tumor endothelial cells (readily accessible from the vascul...


Cell surface Nucleolin represents a novel cellular target for neuroblastoma the...

Brignole, Chiara; Bensa, Veronica; Fonseca, Nuno A.; Del Zotto, Genny; Bruno, Silvia; Cruz, Ana F.; Malaguti, Fabiana; Carlini, Barbara; Morandi, Fabio

Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Nucleolin (NCL) is a protein overexpressed and partially localized on the cell surface of tumor cells of adult cancers. Little is known about NCL and pediatric tumors and nothing is reported about cell surface NCL and NB. Methods: NB cell lines, Schwannian stroma-poor NB tumors and bone marrow (BM)-infilt...


The Enhanced Efficacy of Intracellular Delivery of Doxorubicin/C6-Ceramide Comb...

Cruz, Ana F.; Caleiras, Mariana B.; Fonseca, Nuno A.; Gonçalves, Nélio; Mendes, Vera M.; Sampaio, Susana F.; Moura, Vera; Melo, Joana B.

Targeting multiple cellular populations is of high therapeutic relevance for the tackling of solid tumors heterogeneity. Herein, the ability of pegylated and pH-sensitive liposomes, functionalized with the nucleolin-binding F3 peptide and containing doxorubicin (DXR)/C6-ceramide synergistic combination, to target, in vitro, ovarian cancer, including ovarian cancer stem cells (CSC), was assessed. The underlying ...


Engineered exosome-mediated delivery of RNAi therapeutics towards triple negati...

Ferreira, Débora; Costa, Marta; Baltazar, Fátima; Kalluri, Raghu; Moreira, João N.; Rodrigues, L. R.

[Excerpt] Breast cancer was the leading cause of global cancer incidence in 2020, with an estimated 2.3 million new diagnosed cases among women. Triple negative breast cancer (TNBC) characterized by the absence of hormone receptors, lack of expression of epidermal growth factor receptor-2 and poor prognosis, represents about 10-20% of all breast cancers. Hence, an efficient targeted delivery system is urgently ...


Surface engineering of exosomes led to an enhanced uptake by triple negative br...

Ferreira, Débora; Moreira, João N.; Rodrigues, L. R.

[Excerpt] Background: Triple negative breast cancer (TNBC) represents 10-20% of all breast cancer cases and is characterized by an aggressive progression with metastatic nature and high rates of relapse [1]. Due to a lack of known specific molecular biomarkers for this breast cancer subtype, there are no targeted therapies available, which results in the worst prognosis of all breast cancer subtypes. Hence, the...


Peptide-mediated targeted delivery system towards triple negative breast cancer...

Ferreira, Débora; Moreira, João N.; Kalluri, Raghu; Rodrigues, L. R.

About 2.1 million new diagnosed breast cancer cases among women were estimated for 2018. Triple negative breast cancer (TNBC), characterized by the absence of hormone receptors (estrogen and progesterone), lack of expression of epidermal growth factor receptor-2 and poor prognosis, represents 10-20% of all breast cancers. Hence, the identification of novel biomarkers for this type of breast cancer is highly rel...


Antibacterial activity of chitosan nanofiber meshes with liposomes immobilized ...

Monteiro, Nelson; Martins, Margarida; Martins, Albino; Fonseca, Nuno A.; Moreira, João N.; Reis, R. L.; Neves, N. M.

Chitsan (Ch) nanofiber mesh (NFM) is a material with natural characteristics favoring its use in human wound dressing. The present work proposes a gentamicin-loaded liposome immobilized at the surface of Ch NFMs to promote its antibacterial activity. To achieve this purpose, Ch NFMs were functionalized with thiol groups, and gentamicin-loaded liposomes were covalently immobilized by the reaction of the SH group...


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