A cascade dual-targeted nanocarrier for enhanced alectinib delivery to ALK-positive lung cancer.

Abstract

Alectinib is a highly efficacious inhibitor for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in the clinic; however, serious adverse events (AEs) occurred in 44.0% of patients. Herein, we explored magnetic/TAT dual-targeted nanocarriers as delivery systems for alectinib. Magnetic targeting efficiently enhanced the extravasation of alectinib-loaded nanoparticles from vessels into the tumor tissue, while the TAT targeting reactivated in the tumor tissue significantly improved the tumor cellular uptake of the nanocarrier. As a result, this dual-targeted polymeric nanocarrier exhibited superior therapeutic effects and induced tumor shrinkage in vivo. Meanwhile, this dual-targeted nanocarrier also minimized alectinib-induced hepatotoxicity, providing an efficient strategy to extend the application of alectinib for NSCLC patients.

• Authors: Fanjun Zeng , Bin Xu , Hongyuan Zhu , Shaowei Wu , Guoqing Liao , Daipeng Xie , Luyu Huang , Guibin Qiao , Xianzhu Yang , Haiyu Zhou
• Journal: Biomaterials science (Biomater Sci) Vol. 8 Issue 22 Pg. 6404-6413 (Nov 21 2020) ISSN: 2047-4849 [Electronic] England
• PMID: 33047769 (Publication Type: Journal Article)

Chemical References

• Carbazoles
• Piperidines
• Protein Kinase Inhibitors
• Anaplastic Lymphoma Kinase
• alectinib

Topics

• Anaplastic Lymphoma Kinase (genetics)
• Carbazoles
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Humans
• Lung Neoplasms (drug therapy)
• Piperidines
• Protein Kinase Inhibitors