RESUMO
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.
Assuntos
Oligopeptídeos/química , Peptídeos Cíclicos/química , Separação Celular , Compostos Ferrosos/química , Células HEK293 , Humanos , Integrina alfaVbeta3/metabolismo , Metalocenos , Microscopia , Oxirredução , Peptídeos Cíclicos/metabolismo , Técnicas de Microbalança de Cristal de Quartzo , Propriedades de Superfície , beta-Ciclodextrinas/químicaRESUMO
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.
Assuntos
Integrina alfaVbeta3/análise , Metaloproteinase 9 da Matriz/análise , Neoplasias Experimentais/diagnóstico , Neoplasias Experimentais/metabolismo , Oligopeptídeos , Animais , Linhagem Celular Tumoral , Fluorescência , Células HEK293 , Humanos , Integrina alfaVbeta3/biossíntese , Integrina alfaVbeta3/metabolismo , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/química , Oligopeptídeos/administração & dosagem , Oligopeptídeos/químicaRESUMO
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.
Assuntos
Doenças do Gato/cirurgia , Fibrossarcoma/veterinária , Integrina alfaVbeta3/análise , Animais , Doenças do Gato/metabolismo , Gatos , Feminino , Fibrossarcoma/metabolismo , Fibrossarcoma/radioterapia , Fibrossarcoma/cirurgia , Imunofluorescência/métodos , Imunofluorescência/veterinária , Aumento da Imagem/métodos , Integrina alfaVbeta3/metabolismo , Masculino , Sondas Moleculares , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Espectroscopia de Luz Próxima ao Infravermelho/veterinária , Distribuição TecidualRESUMO
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.
