Novel Integrin αvβ3-Specific Ligand for the Sensitive Diagnosis of Glioblastoma.

Abstract

Integrin αvβ3 is a cell adhesion molecule involved in the progression and invasion of glioblastoma, making it an attractive target for the diagnosis of glioblastoma. Although some integrin αvβ3 specific ligands, such as RGD and its mimetic peptides (Cilengitide), have been devoted in detecting glioblastoma, their clinical practices have been limited due to low specificity and affinity. Herein, we have identified a linear peptide RWrNK, containing an unnatural d-arginine (r), as the integrin αvβ3-specific ligand. RWrNK shows high binding affinity to integrin αvβ3 with a Kd value of 1.6 nM, which is 2-fold higher than Cilengitide (3.2 nM), a well-established integrin αvβ3 ligand. In addition, RWrNK can not only rapidly transport in human glioblastoma U87MG cells but effectively label U87MG tumor spheroids, compared to Cilengitide, indicating that it possesses an ability to sensitively detect glioblastoma. Importantly, RWrNK can pass through blood-brain tumor barrier (BBTB) and selectively accumulate in orthotopic U87MG tumor within 2 h, allowing for imaging glioblastoma in vivo with high sensitivity and specificity. Overall, RWrNK has the great potential in theranostic applications for glioblastoma, in consideration of its high specificity and affinity for integrin αvβ3.

• Authors: Lei Zhang, Xue Shan, Xia Meng, Tingting Gu, Leilei Guo, Xueying An, Qing Jiang, Haixiong Ge, Xinghai Ning
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 16 Issue 9 Pg. 3977-3984 (09 03 2019) ISSN: 1543-8392 [Electronic] United States
• PMID: 31306580 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Integrin alphaVbeta3
• Ligands
• Oligopeptides
• Snake Venoms
• Cilengitide
• arginyl-glycyl-aspartic acid

Topics

• Animals
• Blood-Brain Barrier (metabolism)
• Brain Neoplasms (diagnostic imaging, metabolism, pathology)
• Gene Knockout Techniques
• Glioblastoma (diagnostic imaging, metabolism, pathology)
• Human Umbilical Vein Endothelial Cells
• Humans
• Integrin alphaVbeta3 (genetics, metabolism)
• Ligands
• MCF-7 Cells
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Oligopeptides (metabolism)
• Optical Imaging
• Protein Binding
• Snake Venoms (metabolism)
• Transfection
• Xenograft Model Antitumor Assays