Localised Delivery of Cisplatin from Chitosan-Coated Titania Nanotube Array Nanosystems Targeting Nasopharyngeal Carcinoma

Abstract

Pupose: Cisplatin (CDDP), while amongst the most widely used chemotherapeutic drugs currently available, is well known to have a number of limitations, such as the lack of a single treatment approach and non-specific targeted therapies. Therefore, the development of an innovative strategy that could achieve localised CDDP treatment is an urgent undertaking. Recent advances in titania nanotube arrays (TNA) technology have demonstrated promising applications for localised chemotherapeutic drug treatment. The present work investigated the efficiency of a TNA nanosystem for the localised CDDP treatment of nasopharyngeal carcinoma (NPC). Methods: Two models of the TNA nanosystem were prepared: one consisted of CDDP loaded onto the TNA nanosystem surface (CDDP-TNA) and the other consisted of chitosan-coated CDDP-TNA. CDDP release from these two systems was comprehensively tested on the NPC cell lines NPC/HK-1 and C666-1. The NPC cytotoxicity profile of the two CDDP-TNA nanosystems was evaluated after incubation for 24, 48 and 72 h. Intracellular damage profiles were studied using fluorescence staining microscopic analysis with Hoechst 33342, acridine orange and propidium iodide. Results: The half-maximal inhibitory concentrations (IC50) of CDDP at 24 h were 0.50 mM for NPC/HK-1 and 0.05 mM for C666-1. CDDP in the CDDP-TNA and chitosan-coated CDDP-TNA models presented a significant degree of NPC inhibition (p < 0.05) after 24, 48 and 72 h of exposure. Fluorescence microscopy images revealed cellular damage and shrinkage of the cell membranes after 48 h of exposure to CDDP-TNA. Conclusion: This in vitro work demonstrated the effectiveness of TNA nanosystems for the localised CDDP treatment of NPC cells. Further in vivo studies are needed to support the findings.