UHMSNMRI · Design and testing of Gd3+-Loaded Ultrasmall Hollow Mesoporous Silica Nanosphere Platform as High Sensitivity Probes for Targeted Magnetic Resonance Imaging of Tumor In Vivo
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2013-01-28 → 2015-01-27
- Финансиране от ЕС
- 193 727 €
- Участници
- 1
- Схема
- MC-IIF
Линиите свързват координатора с партньорите.
Накратко на български
Специални наночастици от силициев диоксид с гадолиний се тестват за по-точното откриване на тумори, например при глиоми в мозъка. Те помагат за повишаване на чувствителността на магнитно-резонансния образ, което улеснява визуализирането на раковите клетки в организма.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Design and testing of Gd3+-Loaded Ultrasmall Hollow Mesoporous Silica Nanosphere Platform as High Sensitivity Probes for Targeted Magnetic Resonance Imaging of Tumor In Vivo
Magnetic resonance imaging (MRI) has become a powerful technique in diagnostic clinical medicine and biomedical research by providing long-term, high spatial resolution images of soft tissue without exposing to ionizing radiation. However, MRI still suffers from a relatively low sensitivity and in one third of all MRI clinic scans contrast agents (CAs) are needed. Therefore, the development of highly efficient CAs has been an object of great interest to improve the MR sensitivity. Herein, we developed a targeting, high relaxivity, fluorimagnetic nanoprobe based on fluorescein-doped and amino-functionalized small size mesoporous silica nanoparticles (MSNs) (~ 30 nm). The fluorescein dye (FITC) was embedded in the framework of the silica by co-condensation with a modified silicate source, endowing the MSNs with fluorescent properties in order to visualize the interaction of the MSNs with cells. The MSNs surface was further functionalized with macrocyclic Gd-complexes: Gd-DOTAGA and the αvβ3 integrin targeting ligand RGD peptide. The final nanoprobe (Gd-MSNs-RGD) showed good physiological stability and high relaxivity (37.6 mM-1s-1 at 21.5 MHz). The cytotoxicity and targeting capability of the Gd-MSNs-RGD nanoprobes were first evaluated in human malignant gliomas U87MG cells (which overexpress integrin αvβ3 receptors) by fluorescence and MR imaging. The Gd-MSNs-RGD showed very low cytotoxicity and highly specificity binding affinity to integrin-positive U87MG cells in vitro. Then, the Gd-MSNs-RGD nanoprobes were tested fro the visualization of xenografts tumor models. The in vivo MR images clearly highlighted the tumor from 1 to 6 hours after intravenous administration. These results were further confirmed by the ex vivo fluorescence imaging of major organs. In conclusion, our results have successfully demonstrated the application of integrin αvβ3 targeting Gd-MSNs-RGD for high sensitive multifunctional imaging studies, from the cellular scale to small-animal whole-body evaluation.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The widespread use of magnetic resonance imaging (MRI) technology in clinical and scientific research has attracted great interest in designing high relaxivity contrast agents to improve their sensitivity for the early stage detection of cancer. A number of nanostructure-based T1 contrast agents have been reported in recent years but they are still suffering some limitations for an efficient translation to in vivo applications.In this proposal, we’ll develop a novel Gd3+-loaded ultrasmall hollow mesoporous silica nanosphere (Gd-UHMSNs) platform as high sensitivity MRI probes for targeting T1-MRI of small animal tumor xenografts and potentially, of cancer patient. The specific aims for the proposal are (1) synthesize UHMSNs, and design routes to couple the particles with Gd-complexes, PEG, RGD or other targeting vectors ; (2) evaluate the relaxivity, toxicity, specific targeting capabilities of Gd-UHMSNs-RGD through tests in cell culture; and (3) evaluate the targeting agents for MRI detection of tumors in different types of mice models. Compared to the current contrast agents, the Gd-UHMSNs-RGD hopefully will show many advantages such as (1) the nanoporous and hollow structural will offer effective geometrical confinement of the Gd-complex and water molecular for enhances the r1 relaxivity, (2) the small particle size < 50 nm, high dispersivity and low toxicity is expected to avoid the RES uptake and efficiently prolong the half-time of circulation in body, (3) the RGD vectors will allow the accumulation of the particles at the tumor endothelium and at the tumor cells.Success of this project can not only provide theoretical insight to the development of nanoparticle-based high relaxivity and targeting contrast agents, but also guide us to develop a novel contrast agent for pre-scanning patients and personalized nanomedicine, resulting in great commercialization potentials.""
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITA DEGLI STUDI DI TORINO · TorinoКоординаторИталия
Връзки
Данни: CORDIS, © Европейски съюз