Aptamer-Functionalized
ZIF‑8 Nanomedicine for
Targeted Delivery of Gefitinib and siRNA to Treat Tyrosine-Kinase-Inhibitor-Resistant
Nonsmall-Cell Lung Cancer
posted on 2023-11-18, 15:40authored byMeng Liu, Chuanchuan Sun, Jiangle Jiang, Li Wan, Chong Hu, Chunping Wen, Guiju Huang, Qiufen Ruan, Shuang Wu, Dan Qiao, Pengwu Zheng, Qingshan Pan, Wufu Zhu
The epidermal growth factor receptor (EGFR) tyrosine
kinase inhibitor
gefitinib (GEF) has been used to treat nonsmall-cell lung cancer (NSCLC);
yet, the curative effect of GEF was compromised by drug resistance.
Herein, an EGFR aptamer-modified therapeutic strategy (Apt/(siRNA
+ GEF)@ZIF-8 nanoparticles (NPs)) was fabricated by employing zeolitic
imidazolate framework-8 (ZIF-8)-based metal–organic frameworks
for targeted delivery of GEF and EGFR siRNA to suppress the drug-resistant
gene expression in tumors. Apt/(siRNA + GEF)@ZIF-8 NPs had a high
loading efficiency for GEF and siRNA, and the particle size was about
75 nm with a stable crystal structure. In vitro experiments showed
that GEF cooperating with siRNA could promote cell apoptosis and displayed
a synergistic therapeutic effect on drug-resistant cancer cells. In
vivo biodistribution study demonstrated that Apt/(siRNA + GEF)@ZIF-8
could be enriched at tumor sites successfully, which provided a basis
for in vivo antitumor experiments. In vivo experiment illustrated
that the NPs with good biocompatibility had a high efficiency for
conquering the acquired resistance to EGFR tyrosine kinase inhibitors
in NSCLC with a tumor inhibition rate of 40.6%. Overall, the findings
from this study implied that this biological target nanodrug therapy
may provide a promising approach for the treatment of drug-resistant
NSCLC.