Enhancement of radiotherapeutic efficacy for esophageal cancer by paclitaxel-loaded red blood cell membrane nanoparticles modified by the recombinant protein anti-EGFR-iRGD

Abstract

Paclitaxel is widely used as a radiosensitizer for various tumors, including esophageal cancer, but its therapeutic effect remains to be improved. In this study, we constructed a novel nano-radiosensitizer, anti-EGFR-iRGD-conjugated (iE)-PRNPs, by conjugating the recombinant protein anti-epidermal growth factor receptor (EGFR)-internalizing arginine-glycine-aspartic (iRGD) to the surface of paclitaxel-loaded red blood cell membrane nanoparticles (PRNPs). The iE-PRNPs were confirmed to possess tumor-targeting, high penetrability, and sustained release properties that free paclitaxel does not possess. Compared with that of paclitaxel, the sensitizer enhancement ratio of iE-PRNPs was significantly increased (1.32-fold and 1.25-fold) in esophageal cancer cells with high and low expression levels of EGFR, respectively. Additionally, compared with that of unmodified PRNPs, the sensitizer enhancement ratio of iE-PRNPs in EGFR-overexpressing esophageal cancer cells was significantly increased (1.27-fold), while that of PRNPs in esophageal cancer cells with a low EGFR expression level increased slightly (1.06-fold). The improved radiosensitization effect was associated with enhanced G2/M arrest, increased reactive oxygen species, and more effective induction of DNA double-strand breaks. In summary, iE-PRNPs appear to be a novel type of radiosensitizer with the potential to overcome the bottleneck of esophageal cancer radiotherapeutic efficacy.