Published in:
01-03-2016 | Original Article – Cancer Research
Radionuclide therapy using 131I-labeled anti-epidermal growth factor receptor-targeted nanoparticles suppresses cancer cell growth caused by EGFR overexpression
Authors:
Wei Li, Zhongyun Liu, Chengxia Li, Ning Li, Lei Fang, Jin Chang, Jian Tan
Published in:
Journal of Cancer Research and Clinical Oncology
|
Issue 3/2016
Login to get access
Abstract
Introduction
Anti-epidermal growth
factor receptor (EGFR)-targeted nanoparticles can be used to deliver a therapeutic and imaging agent to EGFR-overexpressing tumor cells. 131I-labeled anti-EGFR nanoparticles derived from cetuximab were used as a tumor-targeting vehicle in radionuclide therapy.
Methods
This paper describes the construction of the anti-EGFR nanoparticle EGFR–BSA–PCL. This nanoparticle was characterized for EGFR-targeted binding and cellular uptake in EGFR-overexpressing cancer cells by using flow cytometry and confocal microscopy. Anti-EGFR and non-targeted nanoparticles were labeled with 131I using the chloramine-T method. Analyses of cytotoxicity and targeted cell killing with 131I were performed using the MTT assay. The time-dependent cellular uptake of 131I-labeled anti-EGFR nanoparticles proved the slow-release effects of nanoparticles. A radioiodine therapy study was also performed in mice.
Results
The EGFR-targeted nanoparticle EGFR–BSA–PCL and the non-targeted nanoparticle BSA–PCL were constructed; the effective diameters were approximately 100 nm. The results from flow cytometry and confocal microscopy revealed significant uptake of EGFR–BSA–PCL in EGFR-overexpressing tumor cells. Compared with EGFR–BSA–PCL, BSA–PCL could also bind to cells, but tumor cell retention was minimal and weak. In MTT assays, the EGFR-targeted radioactive nanoparticle 131I–EGFR–BSA–PCL showed greater cytotoxicity and targeted cell killing than the non-targeted nanoparticle 131I–BSA–PCL. The radioiodine uptake of both 131I-labeled nanoparticles, 131I–EGFR–BSA–PCL and 131I–BSA–PCL, was rapid and reached maximal levels 4 h after incubation, but the 131I uptake of 131I–EGFR–BSA–PCL was higher than that of 131I–BSA–PCL. On day 15, the average tumor volumes of the 131I–EGFR–BSA–PCL and 131I–BSA–PCL groups showed a slow growth relationship compared with that of the control group.
Conclusion
The EGFR-targeted nanoparticle EGFR–BSA–PCL demonstrated superior cellular binding and uptake compared with those of the control BSA–PCL. The EGFR-targeted radioactive nanoparticle 131I–EGFR–BSA–PCL exhibited favorable intracellular retention of 131I. Radionuclide therapy using 131I–EGFR–BSA–PCL, which showed excellent targeted cell killing, suppressed cancer cell growth caused by EGFR overexpression.