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Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer

Authors Balasundaram G, Ho CJH, Li K, Driessen W, Dinish US, Wong CL, Ntziachristos V, Liu B, Olivo M

Received 31 August 2014

Accepted for publication 27 September 2014

Published 8 January 2015 Volume 2015:10(1) Pages 387—397

DOI https://doi.org/10.2147/IJN.S73558

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J Webster

Supplementary video depicting the strong photoacoustic signal at the tumor site 3 hours after folate-conjugated polymer dots injection in MCF-7 breast cancer xenograft model.

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Ghayathri Balasundaram,1,* Chris Jun Hui Ho,1,* Kai Li,2 Wouter Driessen,3 US Dinish,1 Chi Lok Wong,1 Vasilis Ntziachristos,3 Bin Liu,2 Malini Olivo1,4

1Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC), 2Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), Singapore; 3Institute of Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany; 4School of Physics, National University of Ireland, Galway, Ireland

*These authors contributed equally to this work


Abstract: Conjugated polymers (CPs) are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA) molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots) in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots) in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve) MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used as a contrast agent for molecular PA diagnostic imaging in various biomedical applications.

Keywords: photoacoustic tomography, conjugated polymers, molecular imaging, breast cancer

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