Engineering EHD1-Targeted Natural Borneol Nanoemulsion Potentiates Therapeutic Efficacy of Gefitinib against Nonsmall Lung Cancer

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.

Bioactive Iridium Nanoclusters with Glutathione Depletion Ability for Enhanced Sonodynamic‐Triggered Ferroptosis‐Like Cancer Cell Death

“…The intracellular ROS level was observed using the DCFH‐DA probe. [ 40 ] As shown in Figure 3b, the groups treated with PBS, HCIr, and US (1.0 W cm −2 , 1.0 MHz, 50% duty cycle, 1 min) displayed negligible green fluorescence, while both the HC + US and HIr + US groups showed moderate fluorescence. In contrast, stronger fluorescence was observed in 4T1 cells after treated with HCIr under US stimulation.…”

Recent Advances in Boosting EGFR Tyrosine Kinase Inhibitors-Based Cancer Therapy

“…Natural borneol, also known as dextrorotatory borneol, was recently used as a chemo-sensitizer to enhance the cytotoxicity of Gefi in A549 NSCLC cells, where natural borneol nanodrug showed enhanced cellular uptake and inhibited EGFRregulatory protein EHD1. 184 3.4. Combination with Autophagy-Inducing/-Inhibition Agents.…”

Natural Products, Alone or in Combination with FDA-Approved Drugs, to Treat COVID-19 and Lung Cancer

“…As regards lung cancer, significant progress has been made in the research of natural product-based nanomedicines [ 163 , 164 ] and combination drug therapies [ 165 , 166 ], which can provide some reference for the related drug discovery and development for COVID-19. In this section, we mainly focused on the nanodrug strategy (containing natural products and FDA-approved drugs) to reveal its unique advantage in the research and development of anti-lung cancer drugs.…”