Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer.

Abstract

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.

• Authors: Zi-Tong Zhao, Jue Wang, Lei Fang, Xin-di Qian, Ying Cai, Hai-Qiang Cao, Guan-Ru Wang, Mei-Lin He, Yan-Yan Jiang, Dang-Ge Wang, Ya-Ping Li
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 44 Issue 1 Pg. 244-254 (Jan 2023) ISSN: 1745-7254 [Electronic] United States
• PMID: 35705687 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.

Chemical References

• Gefitinib
• Bevacizumab
• Vascular Endothelial Growth Factor A
• Quinazolines
• Protein Kinase Inhibitors

Topics

• Humans
• Carcinoma, Non-Small-Cell Lung (metabolism)
• Gefitinib
• Bevacizumab (therapeutic use)
• Lung Neoplasms (pathology)
• Vascular Endothelial Growth Factor A
• Molecular Targeted Therapy
• Quinazolines (pharmacology)
• Drug Resistance, Neoplasm
• Cell Line, Tumor
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Tumor Microenvironment