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Bypassing pro-survival and resistance mechanisms of autophagy in EGFR-positive lung cancer cells by targeted delivery of 5FU using theranostic Ag <sub/>2</sub> S quantum dots

DOI:10.1039/c9tb01602c 期刊:Journal of Materials Chemistry B 出版年份:2019 更新时间:2025-09-16 10:30:52
摘要: Targeted drug delivery systems that combine imaging and therapeutic functions in a single structure have become very popular in nanomedicine. Near-infrared (NIR) emitting Ag2S quantum dots (QDs) are excellent candidates for this task. Here, we have developed PEGylated Ag2S QDs functionalized with Cetuximab (Cet) antibody and loaded with an anticancer drug, 5-fluorouracil (5FU). These theranostic QDs were used for targeted NIR imaging and treatment of lung cancer using low (H1299) and high (A549) Epidermal Growth Factor Receptor (EGFR) overexpressing cell lines. The Cet conjugated QDs effectively and selectively delivered 5FU to A549 cells and provided significantly enhanced cell death associated with apoptosis. Interestingly, while treatment of cells with free 5FU activated autophagy, a cellular mechanism conferring resistance to cell death, these EGFR targeting multimodal QDs significantly overcame drug resistance compared to 5FU treatment alone. The improved therapeutic outcome of 5FU delivered to A549 cells by Cet conjugated Ag2S QDs is suggested as the synergistic outcome of enhanced receptor mediated uptake of nanoparticles, and hence the drug, coupled with suppressed autophagy even in the absence of addition of an autophagy suppressor.
作者: Fatma Demir Duman,Yunus Akkoc,Gozde Demirci,Nima Bavili,Alper Kiraz,Havva Yagci Acar,Devrim Gozuacik
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To develop PEGylated Ag2S quantum dots functionalized with Cetuximab antibody and loaded with 5-fluorouracil for targeted NIR imaging and treatment of EGFR-positive lung cancer cells, overcoming drug resistance mechanisms associated with autophagy.

PEGylated Ag2S QDs functionalized with Cetuximab and loaded with 5FU effectively target EGFR-positive lung cancer cells, enhancing drug delivery and overcoming autophagy-mediated drug resistance. This theranostic approach combines imaging and therapeutic functions, offering a promising strategy for lung cancer treatment.

The study is limited to in vitro experiments; in vivo efficacy and toxicity studies are needed. The specificity and efficiency of drug delivery to EGFR-positive cells in a complex biological environment remain to be fully explored.

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