Inhibitory effect of 131I-labeled epidermal growth factor receptor-targeted liposome nanoparticle on EGFR-overexpressing cancer cells in vitro

Abstract

Objective To construct 131I labeled anti-EGFR immunoliposome nanoparticle (131I-Cetuaximab (C225)-BSA-PCL), and investigate its inhibitory effect on EGFR-overexpressing cancer cells in vitro. Methods Anti-EGFR liposome nanoparticle C225-BSA-PCL and non-targeted liposomes BSA-PCL were constructed. The products were observed with transmission electron microscopy and dynamic light scattering. The EGFR-targeted binding and cellular uptake in EGFR-overexpressing cancer cells were observed with flow cytometry and confocal microscopy. Anti-EGFR and non-targeted liposomes were labeled with 131I using the chloramine-T method. The targeted cell killing effects of 131I labeled liposomes were analyzed using MTT assay. The time-dependent cellular uptake analysis was used to evaluate the slow-release effects of the 131I labeled liposomes. The independent-samples t test was used for data analysis. Results The EGFR-targeted liposome C225-BSA-PCL and non-targeted liposome BSA-PCL were successfully constructed, and the effective diameters were approximately 130-180 nm. Flow cytometry and confocal microscopy revealed significant uptake of C225-BSA-PCL in EGFR-overexpressing tumor cells. BSA-PCL could also bind to cells with minimal and weak tumor retention. The EGFR-targeted radioactive liposome 131I-C225-BSA-PCL showed greater targeted cell killing effect than non-targeted liposome 131I-BSA-PCL, the IC50 values of 131I-C225-BSA-PCL and 131I-BSA-PCL were 0.03-1.32 and 0.25-12.19, respectively. The uptakes of 131I-C225-BSA-PCL was higher than that of 131I-BSA-PCL (t=3.03-16.86, all P<0.05) and reached the maximal level at 4 h after incubation. Conclusions The EGFR-targeted liposome C225-BSA-PCL demonstrated superior cellular binding and uptake on EGFR-overexpressing cancer cells compared with BSA-PCL. The EGFR-targeted radioactive liposome 131I-C225-BSA-PCL had favorable intracellular retention and excellent targeted cell killing effect, and could effectively suppress the growth of EGFR-overexpressing cancer cells. Key words: Liposomes; Nanotechnology; Receptors, epidemal growth factor-urogastrone; Iodine radioisotopes; Tumor cells, cultured