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

Abstract

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 angio genesis

Acknowledgments

We are very grateful to the National Natural Science Foundation of China (81401466 and 81501521) and General project of the frontier and application basic research plan of Chongqing (cstc2015jcyjA1338) for financial support.

Disclosure

The authors report no conflicts of interest in this work.