ABSTRACT
A quartz crystal microbalance technique with dissipation monitoring and a complementary optical microscopy technique were used for monitoring the capture and release of specific cells on a surface displaying a bifunctional molecular device, composed of a molecular scaffold endowed with the cell recognition property of an RGD ligand and a ß-CD/Fc redox-switchable system.
Subject(s)
Oligopeptides/chemistry , Peptides, Cyclic/chemistry , Cell Separation , Ferrous Compounds/chemistry , HEK293 Cells , Humans , Integrin alphaVbeta3/metabolism , Metallocenes , Microscopy , Oxidation-Reduction , Peptides, Cyclic/metabolism , Quartz Crystal Microbalance Techniques , Surface Properties , beta-Cyclodextrins/chemistryABSTRACT
A fluorescent clustered RGD-containing ligand encompassing an MMP substrate was designed and successfully used in vivo for the dual-targeting of α(V)ß(3) integrin receptors and MMP-9 extracellular proteases in the tumor region.
Subject(s)
Integrin alphaVbeta3/analysis , Matrix Metalloproteinase 9/analysis , Neoplasms, Experimental/diagnosis , Neoplasms, Experimental/metabolism , Oligopeptides , Animals , Cell Line, Tumor , Fluorescence , HEK293 Cells , Humans , Integrin alphaVbeta3/biosynthesis , Integrin alphaVbeta3/metabolism , Matrix Metalloproteinase 9/chemistry , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Nude , Molecular Structure , Neoplasms, Experimental/chemistry , Oligopeptides/administration & dosage , Oligopeptides/chemistryABSTRACT
We investigated how near-infrared imaging could improve highly infiltrative spontaneous fibrosarcoma surgery in 12 cats in a clinical veterinary phase. We used an RGD-based nanoprobe at different doses and times before surgery and a portable clinical grade imaging system. All tumours were labelled by the tracer and had an overall tumour-to-healthy tissue ratio of 14±1 during surgery. No false negatives were found, and the percentage of tumour cells was linearly correlated with the fluorescence intensity. All cats recovered well and were submitted to long-term follow-up that is currently on-going 1year after the beginning of the study.
Subject(s)
Cat Diseases/surgery , Fibrosarcoma/veterinary , Integrin alphaVbeta3/analysis , Animals , Cat Diseases/metabolism , Cats , Female , Fibrosarcoma/metabolism , Fibrosarcoma/radiotherapy , Fibrosarcoma/surgery , Fluorescent Antibody Technique/methods , Fluorescent Antibody Technique/veterinary , Image Enhancement/methods , Integrin alphaVbeta3/metabolism , Male , Molecular Probes , Spectroscopy, Near-Infrared/methods , Spectroscopy, Near-Infrared/veterinary , Tissue DistributionABSTRACT
Integrin α(v)ß(3) expression is upregulated during tumor growth and invasion in newly formed endothelial cells in tumor neovasculature and in some tumor cells. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin α(v)ß(3) in vitro and in vivo. When labeled with indium-111, the RAFT-RGD is partially reabsorbed and trapped in the kidneys, limiting its use for further internal targeted radiotherapy and imaging investigations. We studied the effect of Gelofusine on RAFT-RGD renal retention in tumor-bearing mice. Mice were imaged using single photon emission computed tomography and optical imaging 1 and 24 h following tracer injection. Distribution of RAFT-RGD was further investigated by tissue removal and direct counting of the tracer. Kidney sections were analyzed by confocal microscopy. Gelofusine significantly induced a >50% reduction of the renal reabsorption of (111)In-DOTA-RAFT-RGD and A700-RAFT-RGD, without affecting tumor uptake. Injection of Gelofusine significantly reduced the renal retention of labeled RAFT-RGD, while increasing the tumor over healthy tissue ratio. These results will lead to the development of future therapeutic approaches.
