Ana Catarina da SIlva Pacheco
@i3s.up.pt
i3S - Instituto de Investigação e Inovação em Saúde
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Rui Pedro Moura, Catarina Pacheco, Paulo Faria, and Bruno Sarmento
Elsevier
Cláudia Martins, Catarina Pacheco, Paulo Faria, and Bruno Sarmento
Future Medicine Ltd
Cláudia Martins, Marco Araújo, Alessio Malfanti, Catarina Pacheco, Stuart J. Smith, Bernard Ucakar, Ruman Rahman, Jonathan W. Aylott, Véronique Préat, and Bruno Sarmento
Wiley
Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis-driven stimuli-responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, with multifunctional features that circumvent insufficient blood-brain barrier (BBB) trafficking and lack of GBM targeting-two major hurdles for anti-GBM therapies. NPs are dual-surface tailored with a i) brain-targeted acid-responsive Angiopep-2 moiety that triggers NP structural rearrangement within BBB endosomal vesicles, and ii) L-Histidine moiety that provides NP preferential accumulation into GBM cells post-BBB crossing. In tumor invasive margin patient cells, the stimuli-responsive multifunctional NPs target GBM cells, enhance cell uptake by 12-fold, and induce three times higher cytotoxicity in 2D and 3D cell models. Moreover, the in vitro BBB permeability is increased by threefold. A biodistribution in vivo trial confirms a threefold enhancement of NP accumulation into the brain. Last, the in vivo antitumor efficacy is validated in GBM orthotopic models following intratumoral and intravenous administration. Median survival and number of long-term survivors are increased by 50%. Altogether, a preclinical proof of concept supports these stimuli-responsive multifunctional NPs as an effective anti-GBM multistage chemotherapeutic strategy, with ability to respond to multiple fronts of the GBM microenvironment.
Paulo Faria, Catarina Pacheco, Rui Pedro Moura, Bruno Sarmento, and Cláudia Martins
Springer Science and Business Media LLC
Catarina Pacheco, Ana Baião, Tao Ding, Wenguo Cui, and Bruno Sarmento
Elsevier BV
Cláudia Martins, Catarina Pacheco, and Bruno Sarmento
Elsevier
Cláudia Martins, Catarina Pacheco, Catarina Moreira-Barbosa, Ângela Marques-Magalhães, Sofia Dias, Marco Araújo, Maria J. Oliveira, and Bruno Sarmento
Elsevier BV
Catarina Pacheco, Fátima Baltazar, Bruno M. Costa, and Bruno Sarmento
Elsevier BV
Catarina Pacheco, Ana Baião, Flávia Sousa, and Bruno Sarmento
Elsevier
Rui Pedro Moura, Catarina Pacheco, Ana Paula Pêgo, Anne des Rieux, and Bruno Sarmento
Elsevier BV
Catarina Pacheco, Flávia Sousa, and Bruno Sarmento
Elsevier BV