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 T 1 /T 2 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 T 1 and T 2 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 (MnFe 2 O 4 ) nanoparticle core. The results showed that the hydrophobic MnFe 2 O 4 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 MnFe 2 O 4 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 T 2 -weighted MR imaging. With the passage on, the Mn 2+ ions were released from MnFe 2 O 4 and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T 1 -weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe 2 O 4 can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T 1 - and T 2 -enhanced MR imaging of tumor angiogenesis.

SPIO-loaded nanostructured lipid carriers as liver-targeted molecular T2-weighted MRI contrast agent

“…Magnetic resonance imaging (MRI), because of its high spatial, high temporal resolution, non-ionizing radiation and multiparameter imaging, is widely used in clinical diagnosis and research as a non-invasive and effective imaging technique, especially for early cancer diagnosis (1,2). In order to provide more detailed abnormality images and to distinguish diagnostic interest regions from background Original Article SPIO-loaded nanostructured lipid carriers as liver-targeted molecular T2-weighted MRI contrast agent tissues, magnetic resonance contrast agents (MRCAs) are widely utilized (3)(4)(5).…”

Metabolic Conversion and Removal of Manganese Ferrite Nanoparticles in RAW264.7 Cells and Induced Alteration of Metal Transporter Gene Expression

“…Because of the impressive T 1 /T 2 relaxivity, Mn-IONPs have been widely studied and regarded as potential CAs to improve the sensitivity and specificity of molecular MRI. 36 , 39 , 40 In addition, benefiting from the nano scale, Mn-IONPs can be easily engineered and functionalized, making them capable and dispersible agents for drug delivery and hyperthermia therapy. 41 , 42 Even though Mn-IONPs have been studied in biomedicine for several years, there is a poor understanding of the nano-bio interaction of Mn-IONPs at the cellular levels.…”

“…To convert the hydrophobic surface of the Mn-IONPs to a hydrophilic surface, the NPs were treated with TMAH following a previously reported procedure. 36 TEM (Hitachi HT-7700, Hitachi, Tokyo, Japan) was used to determine the morphology and size distribution of the prepared NPs. XRD (PANalytical X’Pert Powder, Almelo, Netherlands) was used to confirm the crystal structure, XPS (ESCALAB 250Xi, Waltham, MA, USA) and ICP-OES (iCAP 6300 Duo, Waltham, MA, USA) were used to detect the elemental composition of the Mn-IONPs and the concentrations of Fe and Mn in the NPs suspensions, respectively.…”

<p>Synthesis Of PEG-Coated, Ultrasmall, Manganese-Doped Iron Oxide Nanoparticles With High Relaxivity For T₁/T₂ Dual-Contrast Magnetic Resonance Imaging</p>

“…Thus far, multifarious CAs have been reported for T 1 /T 2 dual-contrast MRI. A common strategy for the synthesis of T 1 /T 2 dual-contrast CA is to integrate T 1 and T 2 signal moieties as hybrid nanoparticles 17–23. However, due to the magnetic coupling effect, the enhancement generated by the T 1 and T 2 moieties will interact with each other, leading to the compromise of both r 1 and r 2 .…”