Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.

Abstract

AIM:

This study aims to develop new nanoformulations of EGFR T790M targeted inhibitor AZD9291 and paclitaxel (PTX) for combination therapy of lung cancer.

MATERIALS & METHODS:

We prepared and characterized PTX- and AZD9291-loaded disulfide cross-linking micelles (DCMs), and evaluate their combination effect and toxicity in vitro and in lung cancer-bearing mice.

RESULTS:

Drug-loaded DCMs were relatively small in size, and possessed glutathione-responsive drug release. The combination of PTX-DCMs and AZD92921-DCMs exhibited strong synergistic effects in both cell line and in vivo without additional toxicity. Molecular studies demonstrated the synergistic modification in both IKB-α/NF-κB/Bcl-2 and EGFR/Akt pathways.

CONCLUSION:

The combination of DCM-loaded AZD9291 and PTX could potentially offer more effective and less toxicity treatment options for lung cancer patients.

• Authors: Xin-Shuai Wang, Li Zhang, Xiaocen Li, De-Jiu Kong, Xiao-Chen Hu, Xue-Zhen Ding, Jun-Qiang Yang, Meng-Qi Zhao, Yixuan He, Kit S Lam, She-Gan Gao, Tzu-Yin Lin, Yuanpei Li
• Journal: Nanomedicine (London, England) (Nanomedicine (Lond)) Vol. 13 Issue 10 Pg. 1107-1120 (05 2018) ISSN: 1748-6963 [Electronic] England
• PMID: 29874151 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Acrylamides
• Aniline Compounds
• osimertinib
• Paclitaxel

Topics

• Acrylamides (administration & dosage, chemistry)
• Aniline Compounds (administration & dosage, chemistry)
• Animals
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (chemistry, drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Delivery Systems
• Drug Liberation
• Drug Resistance, Neoplasm (genetics)
• Humans
• Mice
• Paclitaxel (administration & dosage, chemistry)
• Xenograft Model Antitumor Assays