Proteomic analysis on cellular response induced by nanoparticles reveals the nano-trafficking pathway through epithelium

doi:10.5246/jcps.2021.02.009

Journal of Chinese Pharmaceutical Sciences ›› 2021, Vol. 30 ›› Issue (2): 107-118.DOI: 10.5246/jcps.2021.02.009

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Proteomic analysis on cellular response induced by nanoparticles reveals the nano-trafficking pathway through epithelium

Jian Zhang¹^,², Mengmeng Qin¹^,², Dan Yang³, Wenbing Dai¹^,², Hua Zhang¹^,², Xueqing Wang¹^,², Bing He¹^,²^,^*(), Qiang Zhang¹^,²^,^*()

1 State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
2 Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
3 School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China

Received:2020-07-11 Revised:2020-08-10 Accepted:2020-08-19 Online:2021-02-28 Published:2021-02-27
Contact: Bing He, Qiang Zhang

Abstract

Abstract:

The application of nanomedicines in oral drug delivery effectively promotes the drug absorption and transportation through enterocytes. Nevertheless, the absence of mechanism studies on efficacy and safety limits their final translation in humans. Although the vesicular trafficking has been verified as the general character for transport of nanomedicines, the deeper mechanism in molecular mechanism is still unclear. Moreover, the cellular transport of nanomedicines is a dynamic process involved by different organelles and components. However, most of existing studies just pay attention to the static location of nanomedicines, but neglect the dynamic biological effects on cells caused by them. Here, we prepared gold nanoparticles (AuNPs) as the model and cultured epithelial cell monolayer to explore the nano-bio interactions at the molecular level. The traditional pharmacological inhibition strategy and subcellular imaging technology elucidated the macropinocytosis/endosome/MVB/lysosome pathway during the transportation of AuNPs. Proteomics strategy based on mass spectrometry (MS) was utilized to identify and quantify proteins involved in the cellular transport of nanomedicines. Multiple proteins related to subcellular structure, signal transduction, energy transformation and metabolism regulation were demonstrated to be regulated by nanoparticle transport. These alterations of protein expression clarified the effects of intracellular proteins and verified the conventional findings. More importantly, it revealed a feedback mechanism of cells to the nano-trafficking. We believed that these new regulatory mechanisms provided new insights into the efficient transport of nanomedicines through epithelial barriers.

Key words: Epithelium, Gold nanoparticles, Intracellular transport, Proteomics, Cellular response

Supporting:

Jian Zhang, Mengmeng Qin, Dan Yang, Wenbing Dai, Hua Zhang, Xueqing Wang, Bing He, Qiang Zhang. Proteomic analysis on cellular response induced by nanoparticles reveals the nano-trafficking pathway through epithelium[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(2): 107-118.

Figures/Tables 11

References 21

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Proteomic analysis on cellular response induced by nanoparticles reveals the nano-trafficking pathway through epithelium

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