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

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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.

Graphical abstract: A cascade dual-targeted nanocarrier for enhanced alectinib delivery to ALK-positive lung cancer

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Article information


Submitted
13 Jun 2020
Accepted
09 Sep 2020
First published
16 Sep 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

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

F. Zeng, B. Xu, H. Zhu, S. Wu, G. Liao, D. Xie, L. Huang, G. Qiao, X. Yang and H. Zhou, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/D0BM00970A

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