Delivery of gefitinib with an immunostimulatory nanocarrier improves therapeutic efficacy in lung cancer.

Abstract

BACKGROUND:

Combining different cancer treatments represents a promising strategy to improve the therapeutic outcome for lung cancer patients with or without druggable gene alterations.

METHODS:

We previously developed a polyethylene glycol-based (PEG-based) immunostimulatory nanocarrier (PEG2k-Fmoc-NLG919) which can efficiently co-deliver an indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor and the chemotherapeutic agent, paclitaxel. This method was found to improve cancer therapy by simultaneously performing immuno- and chemo-therapy. However, whether this nanocarrier could deliver targeted drugs to implement targeted therapy together with immunotherapy remains unclear.

RESULTS:

Here, we report that the delivery of the classical tyrosine kinase inhibitor (TKI), gefitinib, with the optimized PEG5k-Fmoc-NLG919 nanocarrier, increased the sensitivity of lung cancer cells to gefitinib in vitro. Gefitinib was gradually but sufficiently released from the nanocarrier with comparable capacity to inhibit epidermal growth factor receptor (EGFR) activity as using free gefitinib directly. More importantly, treatment with gefitinib-loaded PEG5k-Fmoc-NLG919 could suppress lung tumor development more efficiently than gefitinib alone in vivo by inducing an immune active microenvironment with more functional CD8+ T cells and less regulatory T cell infiltration.

CONCLUSIONS:

Our study therefore demonstrates that delivery of small molecular targeted drugs with the immunostimulatory nanocarrier is a straightforward strategy for improving antitumor response for lung cancer therapy.

• Authors: Dingwei Diao, Jianxue Zhai, Jianjun Yang, Hua Wu, Jianjun Jiang, Xiaoying Dong, Antonio Passaro, Beatrice Aramini, Shuan Rao, Kaican Cai
• Journal: Translational lung cancer research (Transl Lung Cancer Res) Vol. 10 Issue 2 Pg. 926-935 (Feb 2021) ISSN: 2218-6751 [Print] China
• PMID: 33718033 (Publication Type: Journal Article)
• Copyright: 2021 Translational Lung Cancer Research. All rights reserved.