An Activatable Nano‐Prodrug for Treating Tyrosine‐Kinase‐Inhibitor‐Resistant Non‐Small Cell Lung Cancer and for Optoacoustic and Fluorescent Imaging. Issue 38 (19th August 2020)

• Record Type: Journal Article
• Authors: Xie, Xin; Zhan, Chenyue; Wang, Jie; Zeng, Fang; Wu, Shuizhu
• Is Part Of: Small. Volume 16:Issue 38(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-19
• Subjects: celastrol -- fluorescent imaging -- gefitinib -- nano‐prodrugs -- non‐small cell lung cancer -- optoacoustic imaging; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202003451
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer and the cause of high rate of mortality. The epidermal growth factor receptor (EGFR)‐targeted tyrosine kinase inhibitors are used to treat NSCLC, yet their curative effects are usually compromised by drug resistance. This study demonstrates a nanodrug for treating tyrosine‐kinase‐inhibitor‐resistant NSCLC through inhibiting upstream and downstream EGFR signaling pathways. The main molecule of the nanodrug is synthesized by linking a tyrosine kinase inhibitor gefitinib and a near‐infrared dye (NIR) on each side of a disulfide via carbonate bonds, and the nanodrug is then obtained through nanoparticle formation of the main molecule in aqueous medium and concomitant encapsulation of a serine threonine protein kinase (Akt) inhibitor celastrol. Upon administration, the nanodrug accumulates at the tumor region of NSCLC‐bearing mice and releases the drugs for tumor inhibition, and the dye for fluorescence and optoacoustic imaging. Through suppressing the phosphorylation of upstream EGFR and downstream Akt in the EGFR pathway by gefitinib and celastrol, respectively, the nanodrug exhibits high inhibition efficacy against orthotopic NSCLC in mouse models. Abstract : A nano‐prodrug for treating tyrosine‐kinase‐inhibitor‐resistant non‐small cell lung cancer is fabricated. It accumulates in lung tumor and releases two active drugs to effectively inhibit both the upstream and downstream proteins of the epidermal growth factor receptor (EGFR) signaling pathway to achieve high therapeutic efficacy. A near‐infrared (NIR) dye is generated in this process for fluorescence and optoacoustic imaging of drug release.