pH-Responsive chitosan-modified gadolinium oxide nanoparticles delivering 5-aminolevulinic acid: A dual cellular and metabolic T1-T2* contrast agent for glioblastoma brain tumors detection

Diagnosis of glioblastoma multiforme (GBM) with high sensitivity and specificity requires cellular and metabolic imaging. In this study, we aimed to endow gadolinium oxide nanoparticles (Gd2O3 NPs) as an interesting T1 contrast agent with T2* contrast ability through intracellular iron assistance induced by 5-aminolevulinic acid (5-ALA) with ferric ammonium citrate (FAC). Chitosan (CS)-loaded Gd2O3 NPs were loaded with 5-aminolevulinic acid (Gd2O3/[email protected] NPs), and then evaluated as a pH-responsive dual cellular and metabolic T1 and T2* contrast agent for GBM diagnosis. The target NPs with an average size of 138 nm revealed concentration-dependent toxicity against glioblastoma C6 cells. The relaxation rate (R1) of the C6 cells treated with Gd2O3/[email protected] NPs plus FAC was remarkably higher than the controls including Gd2O3/CS-TPP NPs, Gd2O3/[email protected] NPs, and FAC (17.2 ± 2.4 vs. 8 ± 1.5, 8.4 ± 1.2, and 2.3 ± 0.5, respectively). Interestingly, the transverse relaxation rate (R2*) of the C6 cells treated with Gd2O3/[email protected] NPs + FAC was significantly higher than the controls including Gd2O3/CS-TPP NPs, Gd2O3/[email protected] NPs, and FAC (96 ± 8 vs. 25 ± 4, 27 ± 5, and 19 ± 2.6, respectively). We believe that Gd2O3/[email protected] NPs + FAC could be introduced as promising dual cellular and metabolic T1-T2* contrast agents for GBM diagnosis in MRI.