In vivo MR imaging of folate-receptor expression with the folate-specific nanospheres in a C6 glioblastoma model

Abstract

Purpose: To assess the ability of magnetic albumin nanospheres conjugated with folate (FA-MAN) to provide FR-specific enhancement of C6 glioblastoma on magnetic resonance (MR) images.

Procedures: Active targeting effect of magnetic albumin nanospheres conjugated with folate (FA-MAN) was evaluated based on MR images and histopathological analysis. MR imaging of subcutaneously transplanted C6 glioblastomas was performed after intravenous injection of FA-MAN, non-targeted (magnetic albumin nanospheres, MAN) and FA-inhibited (magnetic albumin nanospheres conjugated with folate plus folate, FA-MAN + FA) agents at designated time points. The T₂ relaxation times in tumors were compared among different treatment groups and were correlated with histopathological findings. Prussian blue staining and in vivo toxicology assay were also performed simultaneously.

Results: Upon MR imaging in vivo, T₂ relaxation time of the tumor sites in the group administrated with FA-MAN (T₂ is 49 ms, 46 ms and 45 ms at 24 h, 48 h and 72 h, respectively) has statistical difference compared to those in the groups of MAN (T₂ is 56 ms, 56 ms and 61 ms at 24 h, 48 h and 72 h, respectively) and FA-MAN + FA nanospheres (T₂ is 56 ms, 57 ms and 56 ms at 24 h, 48 h and 72 h, respectively). Prussian blue-stained results demonstrated that more iron particles accumulated in the tumors of the targeted group than those of the other groups. Toxicology assay showed that no noticeable body weight losses were observed after monitoring 31 days, and the results of routine blood parameters, liver and kidney function biomarkers also demonstrated that the nanoshperes did not influence the respectively physiological index. Besides, no obvious pathological injuries on the major organs were examined.

Conclusion: Folate-conjugated magnetic albumin nanospheres were more effective in targeting C6 glioblastoma in vivo.

Keywords:

• Magnetic resonance imaging
• targeting imaging
• folate
• cancer

Acknowledgements

This work was supported by the National Key Basic Research Program of China (973 Program) (Grant No. 2013 CB733803), National Natural Science Foundation of China (81301270, 81271635). The Fundamental Research Funds for the Central Universities and the Regular University Graduate Student Scientific Research Innovation Projects of Jiangsu Province (KYLX_0204), the Scientific Research Foundation of Graduate School of Southeast University and Southeast University Excellent Doctor Degree Thesis Training Fund (YBJJ1459).

Disclosure statement

The author reports no conflicts of interest in this work.

Ethical approval

All applicable institutional and/or national guidelines for the care and use of animals were followed.