Abstract
Despite the effective targeting of the epidermal growth factor receptor (EGFR), the use of gefitinib (GFT) for nonsmall cell lung cancer (NSCLC) treatment meets a failure because of the insufficient drug accumulation in the tumor region. Therefore, developing chemosensitizers of GFT with synergistic therapeutic effects is urgently needed for advanced cancer therapy. Herein, a natural chemosensitizer, natural borneol (NB), is reformulated as an oil-in-water nanoemulsion to enhance its solubility, distribution, and to ultimately increase the therapeutic index with GFT. The nanolization of NB (NBNPs) displays stronger targeted delivery and cytotoxicity than NB by selectively identifying eight specific protein targets in A549 NSCLC cells as revealed by the proteomic studies. Consistently, NBNPs realize stronger chemosensitization effects than NB with GFT by effectively regulating EGFR/EHD1-mediated apoptosis in A549 NSCLC cells. Owing to the satisfying synergistic effect between NBNPs and GFT, the combined therapy not only enhances the anticancer ability of GFT against NSCLC proliferation but also avoids heavy double toxicity in vivo. This finding demonstrates the effective synergism between NBNPs and GFT with clear mechanistic investigation and is expected to extend the application of NBNPs as a novel chemosensitizer for advanced cancer chemotherapy.
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