GSH triggered intracellular aggregated-cisplatin-loaded iron oxide nanoparticles for overcoming cisplatin resistance in nasopharyngeal carcinoma

Abstract

Platinum-based combined chemo-radiotherapy is the most commonly used approach against Nasopharyngeal carcinoma (NPC). However, off target effect and poor efficiency are the two main concerns regarding this approach. Therefore, it is an urgent need to explore novel therapeutic modalities to meet clinically standards. In this work we have established a new anti-cancer drug delivery system, composed of cisplatin (CDDP)-loaded magnetic iron oxide nanoparticles (Fe₃O₄), further functionalized with surface modification of folic acid (FA) and intracellular aggregation ability peptide (Cys(StBu)-Lys-CBT), named as (FA-MNP-CDDP-CBT). FA-MNP-CDDP-CBT was much more effective on the reversal of CDDP resistance with an average reduction in half maximal inhibitory concentration (IC 50) of 40.9% and 59.1% in HNE-1 cells and HNE-1/DDP resistant cells respectively compared to CDDP alone. Moreover, FA-MNP-CDDP-CBT had also shown a superior targeted uptake effect and higher ROS generation. Convincingly, we observed a remarkable increase in the apoptosis rate of NPC cells by using western blot and flow cytometry. Thus, this newly design nano-system provides a facile approach to enhance the antitumor activity by reducing the side effects of chemotherapy, minimizing systemic toxicity, and reversing CDDP treatment resistance, which could be proposed for NPC patients with primary or secondary chemo-resistance in the future.