TAT peptide-modified cisplatin-loaded iron oxide nanoparticles for reversing cisplatin-resistant nasopharyngeal carcinoma

Abstract

As chemo-radiotherapy continues to increase the lifespan of patients with nasopharyngeal carcinoma (NPC), adverse reaction and drug resistance remain two major problems when using cisplatin (CDDP). In this study, we took the lead in designing a dual-mechanism anti-cancer system modified with cell-penetrating peptide on the surface of superparamagnetic iron oxide nanoparticles (SPION) to enhance CDDP delivery efficacy to NPC cells, especially CDDP resistant NPC cells. The combinatorial delivery of CDDP and iron oxide nanoparticles showed an unexpected effect on reversal of CDDP resistance due to the Fenton reaction with an average decrease in the half maximal inhibitory concentration (IC 50) of 85% and 94% in HNE-1/DDP and CNE-2/DDP resistant cells respectively compared to CDDP alone. On this basis, modification with TAT peptide (YGRKKRRQRRR) significantly improved tumor intracellular uptake, devoting to better curative effects and minimized side effects by reducing CDDP therapeutic doses. Furthermore, we specifically labelled CDDP with fluorescence for detection of intracellular nanoparticles uptake and mechanism research through drug tracing. This novel compound provides a promising therapy for reducing chemotherapy side effects and reversing CDDP-resistant nasopharyngeal carcinoma.

Keywords: Cisplatin-resistance; Fenton effect; Iron oxide nanoparticles; Nasopharyngeal carcinoma; TAT peptide.