Lipid-Polymer Hybrid Nanoparticle-Based Combination Treatment with Cisplatin and EGFR/HER2 Receptor-Targeting Afatinib to Enhance the Treatment of Nasopharyngeal Carcinoma.

Abstract

PurposeNasopharyngeal carcinoma (NPC) is one of the most prevalent carcinomas among the Cantonese population of South China and Southeast Asia (responsible for 8% of all cancers in China alone). Although concurrent platinum-based chemotherapy and radiotherapy have been successful, metastatic NPC remains difficult to treat, and the failure rate is high.MethodsThus, we developed stable lipid–polymer hybrid nanoparticles (NPs) containing cisplatin (CDDP) and afatinib (AFT); these drugs act synergistically to counter NPC. The formulated nanoparticles were subjected to detailed in vitro and in vivo analysis.ResultsWe found that CDDP and AFT exhibited synergistic anticancer efficacy at a specific molar ratio. NPs were more effective than a free drug cocktail (a combination) in reducing cell viability, enhancing apoptosis, inhibiting cell migration, and blocking cell cycling. Cell viability after CDDP monotherapy was as high as 85.1%, but CDDP+AFT (1/1 w/w) significantly reduced viability to 39.5%. At 1 µg/mL, AFT/CDDP-loaded lipid–polymer hybrid NPs (ACD-LP) were significantly more cytotoxic than the CDDP+AFT cocktail, indicating the superiority of the NP system.ConclusionThe NPs significantly delayed tumor growth compared with either CDDP or AFT monotherapy and were not obviously toxic. Overall, the results suggest that AFT/CDDP-loaded lipid–polymer hybrid NPs exhibit great potential as a treatment for NPC.