[en] Abstract Background: B2-S22-AFA is a kind of small molecule mimetic polypeptide that can conjugate to epidermal growth factor receptor 2 (HER-2) specifically and has obvious depressant effect on breast cancer cells with overexpressing HER-2. Purpose: This study aims to investigate the specific killing effect of ¹³¹I-labeled B2-S22-AFA on breast cancer cell with overexpressing HER-2. Methods: ¹³¹I-B2-S22-AFA was prepared by using N-bromosuccinimide method to measure the labeling efficiency, radiochemical purity, stability, and immunocompetence. The expression levels of HER-2 in SKBR3 and MDA-MB-231 cells were detected by Immunohistochemistry and Western Blot. The inhibitory rate of B2-S22-AFA on cell growth was observed with epidermal growth factors (EGF) at different concentrations. Five groups i.e, B2-S22-AFA group (B2-S22-AFA final concentration: 1 μg·mL^-1), ¹³¹I-B2-S22-AFA group (¹³¹I-B2-S22-AFA final concentration: 144 kBq/1 μg·mL^-1), ¹³¹I group (¹³¹I final concentration: 144 kBq·mL^-1), negative control group and reagent blank group, were selected for contrast tests with the final concentration of EGF in each group at 5.0 pg·mL^-1. The proliferation and activity of cells were measured by Methyl thiazolyl tetrazolium assay. The inhibitory rates were compared among ¹³¹I-B2-S22-AFA group, B2-S22-AFA group and ¹³¹I group in the growth of the two kinds of cells at different time. Results: 1) HER-2 receptors were strongly expressed in SKBR3 cells while weakly (low) or no expressed in MDA-MB-231 cells. The radiochemical purity, labeling rate and specific activity of ¹³¹I-B2-S22-AFA were 95.0%-97.6%, 64.8%-79.6% and 151.7 MBq·mg^-1, respectively. Radiochemical purity of ¹³¹I-B2-S22-AFA was 95.4%, 93.5%, 91.4%, 88.2% and 77.4% when it was placed at 37 ℃ in serum for 4 h, 12 h, 24 h, 48 h and 72 h, respectively. The maximum binding rates of SKBR3 and MDA-MB-231 cells were (66.47 ± 3.24)% and (3.89 ± 0.81)% (tested for 3 times) respectively. 2) The inhibitory effect of B2-S22-AFA on the growth of SKBR3 cells only in the presence of EGF. 3) The killing effect of ¹³¹I-B2-S22-AFA on SKBR3 cells was significantly stronger than that of B2-S22-AFA and ¹³¹I (p < 0.05), and the inhibitory effect of B2-S22-AFA on the growth of SKBR3 cells was significantly higher than that of ¹³¹I (p < 0.05). ¹³¹I-B2-S22-AFA and B2-S22-AFA had no obvious killing effect on MDA-MB-231 cells. Conclusion: ¹³¹I-B2-S22-AFA can significantly enhance and accelerate the specific killing effect of B2-S22-AFA on breast cancer cells with high HER-2 expression. (authors)

[en] Highlights: • The reactive oxygen species and glutathione dual responsive nanoparticles (PCL-SS@DTX NPs) was prepared. • The PCL-SS@DTX NPs could rapidly and selectively trigger DTX release in tumor sites. • The PCL-SS@DTX NPs presented excellent biosecurity. • The PCL-SS@DTX NPs enhanced anti-tumor effect in vitro and in orthotopic prostate cancer mice. Docetaxel (DTX)-based chemotherapy of prostate cancer is still confronted with significant challenges due to insufficient drug accumulation at the tumor sites and the systemic side effects on normal cells and organs. Tumor microenvironment-responsive nanosized drug delivery systems have shown enormous potential to improve the anticancer efficacy and minimize the systemic side effects of chemotherapeutics. However, most of the currently redox-responsive nanoparticles respond only to single stimuli, which compromise the treatment effect. Hence, inspired by the abundance of reactive oxygen species (ROS) and intracellular glutathione (GSH) in cancer cells, we proposed a unique ROS and GSH dual responsive nanocarrier (PCL-SS) for DTX delivery. The DTX-loaded PCL-SS nanoparticles (PCL-SS@DTX NPs) were not only stable in a normal physiological environment but also rapidly triggered DTX release in prostate cancer cells. In vitro experiments showed that PCL-SS@DTX NPs had robust prostate cancer cell cytotoxicity, induced cell apoptosis, inhibited cell migration and invasion and exhibited satisfactory biocompatibility. In mice bearing orthotopic prostate cancer, PCL-SS@DTX NPs could accumulate in orthotopic tumor sites and then significantly weaken tumor growth by inhibiting prostate cancer cell proliferation and inducing cell apoptosis, without obvious damages to major organs. Overall, this dual responsive nanosized drug delivery system may act as a promising therapeutic option for prostate cancer chemotherapy.