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Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging

Authors Mouffouk F, Simão T, Dornelles DF, Lopes AD, Sau P, Martins J, Abu-Salah KM, Alrokayan SA, Rosa da Costa AM, dos Santos NR

Received 15 July 2014

Accepted for publication 22 September 2014

Published 17 December 2014 Volume 2015:10(1) Pages 63—76

DOI https://doi.org/10.2147/IJN.S71190

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster

Fouzi Mouffouk,1,* Teresa Simão,2,* Daniel F Dornelles,2 André D Lopes,3 Pablo Sau,4 Jorge Martins,2,5 Khalid M Abu-Salah,6 Salman A Alrokayan,6 Ana M Rosa da Costa,3 Nuno R dos Santos2

1Chemistry Department, Faculty of Science, Kuwait University, Safat, Kuwait; 2IBB – Institute for Biotechnology and Bioengineering, CBME – Centre for Molecular and Structural Biomedicine, 3CIQA-Algarve Chemistry Research Center, Department of Chemistry and Pharmacy, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, Faro, Portugal; 4Centro Radiológico Computarizado SA (CERCO), Seville, Spain; 5Department of Biological Sciences and Bioengineering, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, Faro, Portugal; 6King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia

*These authors contributed equally to this work

Abstract: Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI), able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a gadolinium hydrophobic complex (tBuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that tBuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III) content and its small size (35–40 nm) reveals their potential use for early cancer detection by MRI.

Keywords: micelle, pH-sensitive, self-assembly, smart contrast agent, cancer detection


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