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Gastrin-releasing peptide receptor-targeted gadolinium oxide-based multifunctional nanoparticles for dual magnetic resonance/fluorescent molecular imaging of prostate cancer

Authors Cui DT, Lu XD, Yan CG, Liu X, Hou MR, Xia Q, Xu YK, Liu RY

Received 9 April 2017

Accepted for publication 29 July 2017

Published 12 September 2017 Volume 2017:12 Pages 6787—6797


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun

Danting Cui,1 Xiaodan Lu,1 Chenggong Yan,1 Xiang Liu,1 Meirong Hou,1 Qi Xia,2 Yikai Xu,1 Ruiyuan Liu2,3

1Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of China

Abstract: Bombesin (BBN), an analog of gastrin-releasing peptide (GRP), specifically binds to GRP receptors, which are overexpressed in human prostate cancer (PC). Here, we synthesized a BBN-modified gadolinium oxide (Gd2O3) nanoprobe containing fluorescein (Gd2O3-5(6)-carboxyfluorescein [FI]-polyethylene glycol [PEG]-BBN) for targeted magnetic resonance (MR)/optical dual-modality imaging of PC. The Gd2O3-FI-PEG-BBN nanoparticles exhibited a relatively uniform particle size with an average diameter of 52.3 nm and spherical morphology as depicted by transmission electron microscopy. The longitudinal relaxivity (r1) of Gd2O3-FI-PEG-BBN (r1 =4.23 mM–1s–1) is comparable to that of clinically used Magnevist (Gd-DTPA). Fluorescence microscopy and in vitro cellular MRI demonstrated GRP receptor-specific and enhanced cellular uptake of the Gd2O3-FI-PEG-BBN in PC-3 tumor cells. Moreover, Gd2O3-FI-PEG-BBN showed more remarkable contrast enhancement than the corresponding nontargeted Gd2O3-FI-PEG according to in vivo MRI and fluorescent imaging. Tumor immunohistochemical analysis further demonstrated improved accumulation of the targeted nanoprobe in tumors. BBN-conjugated Gd2O3 may be a promising nanoplatform for simultaneous GRP receptor-targeted molecular cancer diagnosis and antitumor drug delivery in future clinical applications.

Keywords: magnetic resonance imaging, gadolinium oxide, bombesin, gastrin-releasing peptide receptor, molecular imaging

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