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

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Abstract
Purpose: Nasopharyngeal 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. Methods: Thus, 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. Results: We 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. Conclusion: The 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.

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