Antitumor Effect of Nanoparticle ¹³¹I-Labeled Arginine-Glycine-Aspartate-Bovine Serum Albumin-Polycaprolactone in Lung Cancer.

Abstract

The aim of the present study is to investigate the biologic effects of internal irradiation and the therapeutic effectiveness of ¹³¹I-labeled arginine-glycine-aspartate (RGD)-bovine serum albumin (BSA)-polycaprolactone (PCL) (¹³¹I-RGD-BSA-PCL) in murine lung cancer models. The target binding and cellular uptake of NCI-H460 lung cancer cells overexpressing integrin α_vβ₃ were observed by confocal microscopy. Flow cytometry was used to assay apoptosis. The biologic effects of internal irradiation and the therapeutic efficacy of ¹³¹I-RGD-BSA-PCL were investigated in murine lung cancer models; tumor size, body weight, histopathologic findings, and SPECT/CT imaging findings were also monitored. In vitro uptake studies performed using confocal microscopy showed that, after 1 hour of incubation with RGD-BSA-PCL or BSA-PCL, visible fluorescence was present in the cells, and after 8 hours, the florescent signal did not disappear. The mean (± SE) tumor uptake level (i.e., the percentage of the injected dose per gram of tissue [% ID/g]) of ¹³¹I-labeled BSA-PCL (¹³¹I-BSA-PCL) at 24 and 72 hours after injection was 11.06% ± 2.15% ID/g and 3.83% ± 0.87% ID/g, respectively, which is significantly higher than the uptake levels noted for other organs (p < 0.05). The level of tumor uptake of ¹³¹I-RGD-BSA-PCL at 24 and 72 hours after injection was 39.49% ± 6.06% ID/g and 6.97% ± 1.43% ID/g, respectively, which is significantly higher than that of ¹³¹I-labeled liposome (p < 0.05). The decrease in body weight in the group treated with ¹³¹I-RGD-BSA-PCL was only 3.5% of the original body weight and was much lower than noted in the group receiving saline (i.e., 21.5% of original body weight). The median survival time for the therapeutic groups was prolonged to 27 days and 23 days after treatment with ¹³¹I-RGD-BSA-PCL and ¹³¹I-BSA-PCL, respectively. RGD-BSA-PCL has excellent cellular binding in vitro in a non-small cell lung cancer xenograft model. Furthermore, ¹³¹I-RGD-BSA-PCL was evaluated as an imaging agent and is an interesting candidate for targeting therapies in the non-small cell lung cancer xenograft model.