An Osimertinib-Perfluorocarbon Nanoemulsion with Excellent Targeted Therapeutic Efficacy in Non-small Cell Lung Cancer: Achieving Intratracheal and Intravenous Administration

Authors：Yang, Jie; Li, Yingbo; Sun, Jiemei; Zou, Hongyan; Sun, Yige; Luo, Jing; Xie, Qian; Rong, A.; Wang, Hongbin; Li, Xiaona; Wang, Kai; Yang, Lili; Ma, Teng^*; Wu, Lina^*; Sun, Xilin^*

Source：ACS Nano, 2022, 16(8): 12590-12605.

DOI：10.1021/acsnano.2c04159

• pulmonary delivery
• perfluorocarbon
• third-generation EGFR-TKI
• low-intensity focused ultrasound
• drug delivery system
• tumor penetration

Low accumulation of anticancer drugs in tumors and serious systemic toxicity remain the main challenges to the clinical efficiency of pharmaceuticals. Pulmonary delivery of nanoscale-based drug delivery systems offered a strategy to increase antitumor activity with minimal adverse exposure. Herein, we report an osimertinib-loaded perfluoro-15-crown-5-ether (AZD9291-PFCE) nanoemulsion, through intratracheal and intravenous delivery, synergizes with 19F magnetic resonance imaging (F-19 MRI)-guided low-intensity focused ultrasound (LIFU) for lung cancer therapy. Pulmonary delivery of AZD9291-PFCE nanoemulsion in orthotopic lung carcinoma models achieves quick distribution of the nanoemulsion in lung tissues and tumors without short-term and long-term toxic effects. Furthermore, LIFU can trigger drug release from the AZD9291-PFCE nanoemulsion and specifically increases tumor vascular and tumor tissue permeability. F-19 MRI was applied to quantify nanoemulsion accumulation in tumors in real time after LIFU irradiation. We validate the treatment effect of AZD9291-PFCE nanoemulsion in resected human lung cancer tissues, proving the translational potential to enhance clinical outcomes of lung cancer therapy. Thus, this work presents a promising pulmonary nanoemulsion delivery system of osimertinib (AZD9291) for targeted therapy of lung cancer without severe side effects.

• Institution
  中国医学科学院; 哈尔滨医科大学; 中国科学院