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真菌生物合成阿霉素偶联氧化锌纳米粒子对肺癌细胞具有高效治疗作用。

Doxorubicin-Conjugated Zinc Oxide Nanoparticles, Biogenically Synthesised Using a Fungus , Exhibit High Therapeutic Efficacy against Lung Cancer Cells.

机构信息

Department of Biosciences, Integral University, Lucknow 226026, India.

Department Biology, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.

出版信息

Molecules. 2022 Apr 18;27(8):2590. doi: 10.3390/molecules27082590.

Abstract

This study reports the therapeutic effectiveness of doxorubicin-conjugated zinc oxide nanoparticles against lung cancer cell line. The zinc oxide nanoparticles (ZnONPs) were first synthesised using a fungus, isolated from air with an extraordinary capability to survive in very high concentrations of zinc salt. Molecular analysis based on 18S rRNA gene sequencing led to its identification as with the NCBI accession no. OL636020. The fungus was found to produce ZnONPs via the reduction of zinc ions from zinc sulphate. The ZnONPs were characterised by various biophysical techniques. ZnONPs were further bioconjugated with the anti-cancer drug doxorubicin (DOX), which was further confirmed by different physical techniques. Furthermore, we examined the cytotoxic efficacy of Doxorubicin-bioconjugated-ZnONPs (DOX-ZnONPs) against lung cancer A549 cells in comparison to ZnONPs and DOX alone. The cytotoxicity caused due to ZnONPs, DOX and DOX-ZnONPs in lung cancer A549 cells was assessed by MTT assay. DOX-ZnONPs strongly inhibited the proliferation of A549 with IC50 value of 0.34 μg/mL, which is lower than IC50 of DOX alone (0.56 μg/mL). Moreover, DOX-ZnONPs treated cells also showed increased nuclear condensation, enhanced ROS generation in cytosol and reduced mitochondrial membrane potential. To investigate the induction of apoptosis, caspase-3 activity was measured in all the treated groups. Conclusively, results of our study have established that DOX-ZnONPs have strong therapeutic efficacy to inhibit the growth of lung cancer cells in comparison to DOX alone. Our study also offers substantial evidence for the biogenically synthesised zinc oxide nanoparticle as a promising candidate for a drug delivery system.

摘要

本研究报告了阿霉素偶联氧化锌纳米粒子对肺癌细胞系的治疗效果。氧化锌纳米粒子(ZnONPs)是使用真菌首次合成的,该真菌从空气中分离出来,具有在极高浓度锌盐中生存的非凡能力。基于 18S rRNA 基因测序的分子分析将其鉴定为具有 NCBI 接入号 OL636020 的。研究发现,真菌通过还原硫酸锌中的锌离子来产生 ZnONPs。ZnONPs 通过各种生物物理技术进行了表征。ZnONPs 进一步与抗癌药物阿霉素(DOX)偶联,这通过不同的物理技术进一步得到证实。此外,我们检查了 Doxorubicin-bioconjugated-ZnONPs(DOX-ZnONPs)与 ZnONPs 和 DOX 单独相比对肺癌 A549 细胞的细胞毒性功效。通过 MTT 测定评估 ZnONPs、DOX 和 DOX-ZnONPs 在肺癌 A549 细胞中引起的细胞毒性。DOX-ZnONPs 强烈抑制 A549 的增殖,IC50 值为 0.34 μg/mL,低于 DOX 单独的 IC50(0.56 μg/mL)。此外,DOX-ZnONPs 处理的细胞还显示出核浓缩增加、细胞质中 ROS 生成增强和线粒体膜电位降低。为了研究诱导凋亡,在所有处理组中测量了 caspase-3 活性。总之,我们的研究结果表明,与 DOX 单独相比,DOX-ZnONPs 具有更强的抑制肺癌细胞生长的治疗效果。我们的研究还为生物合成的氧化锌纳米粒子作为药物输送系统的有前途的候选物提供了实质性证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eb8/9030660/781619d11246/molecules-27-02590-g001.jpg

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