Targeting Mesoporous Silica for Synergistic TH-302 and Afatinib Delivery to Nasopharyngeal Carcinoma

Abstract

Tumor hypoxia is considered as an important factor for tumor metastasis and disease recurrence. Evofosfamide (TH-302) is a hypoxic prodrug, which can selectively target the hypoxic area of solid tumors, and has the potential to improve the efficacy of the commercial anticancer drug afatinib (AFT). However, free hydrophobic AFT and hydrophilic TH-302 still have several unequivocal deficiencies, such as unsatisfactory tumor inhibition rate, serious side effects and being easy to induce multidrug resistance. Moreover, the operation process of co-administration is too complicated. Therefore, this paper discussed the synergistic effects of AFT/TH-302 and developed a kind of co-loaded targeted mesoporous silica nanoparticles (MSNs) for the treatment of nasopharyngeal carcinoma (NPC). The calculated proportion of AFT and TH-302 were encapsulated by folic acid (FA) modified MSNs (FA-MSNs). In vitro experiments showed that free AFT and TH-302 had synergistic effect, while MSNs nanocarrier could significantly reduce the half maximal inhibitory concentrations (IC50) of AFT and TH-302. AFT and TH-302 show significant synergistic on NPC cells, the application of MSN carrier platform including fixed proportion of AFT and TH-302 improves the synergistic effect and provides a new idea for the treatment of NPC.