Radionuclide therapy using 131I-labeled anti-epidermal growth factor receptor-targeted nanoparticles suppresses cancer cell growth caused by EGFR overexpression
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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.
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.
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.
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.
KeywordsEpidermal growth factor receptor Nanoparticles 131I Radioiodine therapy Tumor-targeting
This study was supported by Grants from the National Natural Science Foundation of China (to Jian TAN) (No. 81171372) (to Wei LI) (No. 81301244), Tianjin Research Program of Application Foundation and Advanced Technology (to Tong LIU) (No. 11JCYBJC11700) and the National Key Clinical Specialty Project of China.
Compliance with ethical standards
Conflict of interest
This paper is our own work; we have no specific disclaimers or conflicts of interest.
This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and China Regulations For the Administration of Affairs Concerning Experimental Animals. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Tianjin Medical University General Hospital. All surgery was performed under sodium pentobarbital anesthesia, and all efforts were made to minimize suffering.
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