MR/NIRF Dual-Mode Imaging of αvβ3 Integrin-Overexpressing Tumors Using a Lipopeptide-Based Contrast Agent

Abstract

Early diagnosis and noninvasive detection of hepatocellular carcinoma have profound clinical implications for treatment quality and improved prognosis. To obtain high-resolution macroscopic anatomical information and high-sensitivity microscopic optical signals to detect tumors, it is highly desirable to develop dual-mode magnetic resonance imaging (MRI) and near-infrared fluorescent (NIRF) probes. An MR/NIRF dual-mode targeted contrast agent was created by encapsulating cyclic arginine-glycine-aspartate (cRGD) and Cy5.5 in liposomes and characterized by the particle size distribution, cytotoxicity, targeting, and MRI relaxivity. The MR T2 intensity and fluorescence intensity were evaluated in the tumors, livers, and muscles after the injection of cRGD-Liposome-Cy5.5 and Liposome-Cy5.5 at different time points. The average size of cRGD-Liposome-Cy5.5 was 62.33 ± 4.648 nm. The transverse relaxivity (R2) values had a negative correlation with the concentration of molecular probes. The MR signal intensity was enhanced in tumors after the cRGD-Liposome-Cy5.5 injection and not enhanced in liver parenchyma and muscles at the same time. The fluorescence intensity was enhanced in tumors after cRGD-Liposome-Cy5.5 injection in the targeted group. cRGD -Liposome-Cy5.5 as an entirely organic T2-positive dual-mode MR/NIRF targeted contrast agent is therefore able to detect early-stage hepatocellular carcinoma by targeting integrin αvβ3, providing advantages for potential clinical utility and ease of clinical transformation.

pH‐responsive albumin‐mimetic synthetic nanoprobes for magnetic resonance/fluorescence imaging of thyroid cancer

“…Optical imaging has the characteristics of high sensitivity and strong spatiotemporal resolution, which can be used to guide tumor tissue resection in real‐time and reduce the rate of local recurrence, but the fluorescence penetration depth is limited and it is difficult to provide tomography information 20 . The MR/NIRF dual‐modality molecular imaging technique, which is integrated by magnetic resonance and optical imaging, can effectively overcome the respective shortcomings of the two and realize the complementary advantages, which can provide more comprehensive information for early diagnosis, treatment and monitoring of tumors, and so forth 21‐23 . Currently, many magnetic resonance/optical probes have been successively reported, but the intrinsic dark imaging properties of Fe 3 O 4 , the potential nephrotoxicity of the Ga element, as well as the always present signal of these bimodal probes leading to poor contrast and complex synthesis processes further limit their clinical translation.…”

Evaluation of a Tumor-Targeting Oligosaccharide Nanosystem in BNCT on an Orthotopic Hepatocellular Carcinoma Model

“…On this basis, we take COS as the fundamental material of nanoparticles, and cRGD peptide, which can bind to the integrin αvβ3 overexpressed by tumor cells, is further modified on the COS to realize the active targeting of nanoparticles. 19,20 To effectively kill tumor cells, we combine BNCT and chemotherapy in this article. The carrier loads two drugs.…”

“…It can promote the phagocytosis of nanoparticles by cells as a novel carrier for drug delivery. On this basis, we take COS as the fundamental material of nanoparticles, and cRGD peptide, which can bind to the integrin αvβ3 overexpressed by tumor cells, is further modified on the COS to realize the active targeting of nanoparticles. , …”