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Targeting T1 and T2 dual modality enhanced magnetic resonance imaging of tumor vascular endothelial cells based on peptides-conjugated manganese ferrite nanomicelles

Authors Gong M, Yang H, Zhang S, Yang Y, Zhang D, Li Z, Zou L

Received 20 January 2016

Accepted for publication 16 May 2016

Published 19 August 2016 Volume 2016:11 Pages 4051—4063


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 6

Editor who approved publication: Dr Lei Yang

Mingfu Gong,1 Hua Yang,1,2 Song Zhang,1 Yan Yang,1 Dong Zhang,1 Zhaohui Li,3 Liguang Zou1

1Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of China; 3Geosciences Department, University of Wisconsin-Parkside, Kenosha, WI, USA

Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T1/T2 dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T1 and T2 dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe2O4) nanoparticle core. The results showed that the hydrophobic MnFe2O4 nanoparticles were of uniform spheroidal appearance and narrow size distribution. Due to the self-assembled nanomicelles structure, the prepared probes were of high relaxivity of 281.7 mM-1 s-1, which was much higher than that of MnFe2O4 nanoparticles (67.5 mM-1 s-1). After being grafted with the targeted CD105 peptide CL 1555, the nanomicelles can combine TVECs specifically and make the labeled TVECs dark in T2-weighted MR imaging. With the passage on, the Mn2+ ions were released from MnFe2O4 and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T1-weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe2O4 can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T1- and T2-enhanced MR imaging of tumor angiogenesis.

Keywords: CL 1555, CL-PEG-MnFe2O4, TVECs, CD105, tumor angio­genesis

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