Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/93834
Title: GMP-grade nanoparticle targeted to nucleolin downregulates tumor molecular signature, blocking growth and invasion, at low systemic exposure
Authors: Fonseca, Nuno A.
Gregório, Ana C.
Mendes, Vera M.
Lopes, Rui
Abreu, Teresa 
Gonçalves, Nélio 
Manadas, Bruno 
Lacerda, Manuela 
Figueiredo, Paulo
Pereira, Marta
Gaspar, Manuela
Colelli, Fabiana
Pesce, Daniela
Signorino, Giacomo
Focareta, Laura
Fucci, Alessandra
Cardile, Francesco
Pisano, Claudio
Cruz, Tony 
Almeida, Luís
Moura, Vera 
Simões, Sérgio
Moreira, João N.
Keywords: Nucleolin; Targeted-drug delivery; Mesothelioma; Breast cancer; Nucleolin-overexpressing cancers
Issue Date: Apr-2021
Publisher: Elsevier
Project: POCI-01-0145-FEDER-016390 (acronym: CANCEL STEM) 
Healthy Aging 2020: CENTRO-01-0145-FEDER-000012 
info:eu-repo/grantAgreement/EC/FP7/234811/EU/EUROpean network of trans-national collaborative RTD in the field of NANOMEDicine 
Serial title, monograph or event: Nano Today
Volume: 37
Abstract: 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 vascular compartment), besides cancer cells, with PEGASEMP (doxorubicin hydrochloride in a lipid-based pegylated nanoparticle functionalized with a 31-aminoacid peptide targeting nucleolin), lessens the dependence on high systemic exposures and EPR effect for successful tumor targeting. This strategy has resulted in improved intracellular tumor bioavailability of doxorubicin, at low systemic exposure, associated with a safe toxicological profile. Levels of cell surface nucleolin dictated the antitumor activity of PEGASEMP against nucleolin-overexpressing solid tumors of diverse histological origin, evidencing a significant growth inhibition of malignant mesothelioma over the standard of care. Those observations were paralleled by an impairment of the nucleolin-positive vasculature and downregulation of typically overexpressed genes. Patient stratification based on nucleolin mRNA expression correlated with prognosis and enabled identification of breast and mesothelioma tumors that may potentially benefit from PEGASEMP. Overall, a novel principle of drug delivery is presented with potential therapeutic impact across nucleolin-overexpressing human cancers.
URI: http://hdl.handle.net/10316/93834
ISSN: 17480132
DOI: 10.1016/j.nantod.2021.101095
Rights: embargoedAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat Login
1-s2.0-S1748013221000207-main.pdf15.01 MBAdobe PDFEmbargo Access    Request a copy
Show full item record

Page view(s)

16
checked on Jun 10, 2021

Download(s)

7
checked on Jun 10, 2021

Google ScholarTM

Check

Altmetric

Altmetric


This item is licensed under a Creative Commons License Creative Commons