Targeting therapeutic effect of radioiodine-labeled anti-EGFR binding nanoparticles on glioblastoma cells
2016
Objective
To explore the feasibility of treating glioma with 131I-labeled antiEGFR nanoparticales in vitro and in vivo.
Methods
Radioiodine-labeled anti-EGFR binding nanoparticles were constructed and its in vitro cell-binding ability was confirmed by confocal microscopy and flow cytometry. Cell cytotoxicity of the drug was evaluated by MTT assay. Radioiodine-imaging studies were conducted by using a xenograft nude mouse model in vivo by detecting the change of the volume of the xenograft.
Results
In vitro studies revealed that the anti-EGFR nanoparticles binding with bovine serum albumin-polycaprolactone (anti EGFR-BSA-PCL) or BSA-PCL were successfully constructed. Cells could uptake 131I-antiEGFR-BSA-PCL much more effectively than the 131I-BSA-PCL group. MTT assay indicated that, when the radioactivity approached to 0.925 MBq, the cell growth inhibition rate of 131I-antiEGFR-BSA-PCL was higher than that of 131I-BSA-PCL (U251 cells: t=2.517, P<0.05; U87 cells: t=2.821, P<0.05). The growth inhibition rates at 0.925 MBq was higher than other radioactivity in both U251 cells and U87 cells (131I-antiEGFR-BSA-PCL group: t=2.148, 2.436, P<0.05; 131I-BSA-PCL group: t=2.693, 2.615, P<0.05). Radioactive iodine uptake assay showed that the viability of U251 and U87 cells was reduced after exposure to 0.37 MBq to 3.7 MBq of 131I-antiEGFR-BSA-PCL or 131I-BSA-PCL. The in vivo nude mice experiments disclosed that both kinds of nanoparticles passed by the hepatic metabolism, and the decrease of tumor volume in the group of 131I-antiEGFR-BSA-PCL was more effective than that in the 131I-BSA-PCL group (t=4.115, P<0.05). EGFR significantly enhanced the uptake and accumulation of BSA-PCL in the xenografts nude mice model, indicating an improved nanoparticle-based drug delivery.
Conclusions
131I-antiEGFR-BSA-PCL based radioiodine therapy of U251 and U87 cells had good curative effect in vitro and in vivo. Thus, 131I-antiEGFR-BSA-PCL may provide a new method for glioblastoma treatment.
Key words:
Nanoparticles; Radioiodine-labeled cells; Epidermal growth factor receptor antibody; 131I
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