In vivo and in vitro MR imaging of glioma targeted block copolymer micelles / 中华放射学杂志

ABSTRACT

Objective To explore the in vivo/in vitro MR imaging effect of Angiopep2 modified glioma targeted block copolymer micelles(ANPs/CPT). Methods Angiopep2 modified DOTA-Gd conjugated polymeric micelles based on beta-cyclodextrin(β-CD) were successfully synthesized.Water proton longitudinal relaxation rate (1/T1) were calculated to compare the r1of DOTA-Gd and ANPs/CPT. Different concentration of DOTA-Gd, NP/CPT, ANP/CPT were co-cultured with C6 cells, the intracellular content of Gd3+was analyzed by ICP-AES;The signal intensity(SI) and contrast to noise ratio(CNR) were measured by 1.5 T MR;The CNR of ANPs/CPT was evaluated on different organs of normal rats. The enhancement feature of ANP/CPT in glioma as well as T/N and CNR between tumor and normal brain tissue were also investigated.Several comparisons were made between the 3 groups by one-way ANOVA,and the difference were significant when P<0.05.Results The r1of ANPs/CPT(13.900 s-1·mmol/L-1)was 3 times as much as DOTA-Gd(4.927 s-1·mmol/L-1).C6 cells uptake different concentrations of Gd3 +had significant difference among groups(F=362.502,1636.136,386.880,918.173, P<0.001).The difference of SI and CNR among groups were significant(F=55.240,155.419,P<0.001).The CNR of the brain tissue had significant difference with other organs at all times after tail vein injection of ANPs/CPT(F=9.417,21.808, 21.383,107.318,178.762,P<0.01).The ANPs/CPT showed excellent brain-targeting efficiency and theT/N ratio(30 min after),CNR in different time point had significant difference among groups (F=5.349,6.594,24.078,18.508 and 6.840,6.780,5.895,12.620,37.139,368.893, P<0.05).Conclusions ANPs/CPT shows nice agnetic relaxation performance,extended blood circulation duration,excellent brain-targeting efficieney, which will render the theranosticnano-carriers with important reference for the construction of new generation multifunctional nanomedicine.