Study on angiogenesis-targeting paramagnetic nanoliposomes in MRI for diagnosis of pulmonary carcinoma
10.3781/j.issn.1000-7431.2008.06.009
- Author:
Bo SU
1
Author Information
1. Department of Oncology
- Publication Type:Journal Article
- Keywords:
Lung neoplasms;
Magnetic resonance imaging;
Nanotechnology;
Neovascularization, pathologic;
Paramagnetic
- From:
Tumor
2008;28(6):494-497
- CountryChina
- Language:Chinese
-
Abstract:
Objectives: To construct tumor angiogenesis-targeting paramagnetic liposomes and investigate their potential value as a magnetic resonance imaging (MRI) to detect minute tumor foci in tumor-bearing nude mice. Methods: Peptide-palmitic acid conjugate was prepared using fluorenylmethoxy carbony (Fmoc) solid-phase synthetic method. Angiogenesis-targeting paramagnetic liposome particles were prepared by the thin film dispersion-sonication method. Entrapped efficiency of Gd-DPTA-BMA was determined by centrifugal ultrafiltration. The average size of liposome particles was determined by laser particle sizing analysis. Gd3+ concentration was determined by chlorophosphonazo III colorimetry. The signal enhancement ratio of targeted paramagnetic liposome particles was evaluated by MRI in human lung adenocarcinoma implanted in nude mice. Results: Five paramagnetic liposome particles which targeted αVβ3, vascular endothelial growth factor receptor (VEGFR)-1 and -2 and had different conjugation forms were prepared. Entrapped efficiency of the five prepared paramagnetic liposome particles was from 55.5% to 60.1%, and average particle size was from 109-128 nm. Integrin α V β3 and VEGFR-2-targeted paramagnetic liposome particles showed good tumor-specific MRI signal enhancement in xenograft of the nude mice, especially for Integrin αVβ3 receptor. Spacer 6-aminohexanoic acid demonstrated the better signal enhancement than the other two linkages. Tumor relative signal intensity was increased 1. 8-2. 8 folds than control in T1 weighted MR imaging. Minute tumor nodules (2-5 mm) were clearly identified. Biodistribution analysis showed that the Gd3+ concentration in tumor was significantly higher than that in the heart, lung, liver, and muscle, and slightly higher than that in the spleen and kidney. Conclusion: Angiogenesis-targeting paramagnetic liposome particles were tumor-specific and lasted for a long time. MRI signal enhancement was higher and minute tumor foci (2-5 mm) were clearly identified. It can be developed as a potential tumor-specific MRI contrast agent for the early diagnosis of cancer and metastases.
