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Research Article

AgInS2/ZnS quantum dots for noninvasive cervical cancer screening with intracellular pH sensing using fluorescence lifetime imaging microscopy

Wenhua Su1,§, Dan Yang2,§, Yulan Wang3,§, Yawei Kong1, Wanlu Zhang2, Jing Wang4, Yiyan Fei1, Ruiqian Guo2( ), Jiong Ma1,5,6( ), Lan Mi1,5( )
Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), School of Information Science and Technology, Fudan University, Shanghai 200433, China
Institute for Electric Light Sources, School of Information Science and Technology, Fudan University, Shanghai 200433, China
Department of Gynecology and Obstetrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
Institute of Photonic Chips, University of Shanghai for Science and Technology, Shanghai 200093, China Centre for Artificial-Intelligence Nanophotonics, School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
Institute of Biomedical Engineering and Technology, Academy for Engineer and Technology, Fudan University, 220 Handan Road, Shanghai 200433, China
Shanghai Engineering Research Center of Industrial Microorganisms, the Multiscale Research Institute of Complex Systems (MRICS), School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China

§ Wenhua Su, Dan Yang, and Yulan Wang contributed equally to this work.

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Graphical Abstract

An intracellular pH sensor AgInS2 (AIS)/ZnS quantum dots (QDs) with long fluorescence lifetimesare synthesized, and they exhibit a reduced fluorescence lifetime when in higher pH conditions.AIS/ZnS QDs combined with fluorescence lifetime imaging microscopy (FLIM) are used to evaluatethe ability for human cervical cancer (CC) screening for the first time. The proposed method has greatpromise for the noninvasive screening and diagnosis of CC, and the method may be applied to otherpH-related diseases in the future.

Abstract

Intracellular pH plays a critical role in biological functions, and abnormal pH values are related to various diseases. Here, we report on an intracellular pH sensor AgInS2 (AIS)/ZnS quantum dots (QDs) that show long fluorescence lifetimes of hundreds of nanoseconds and low toxicity. Fluorescence lifetime imaging microscopy (FLIM) combined with AIS/ZnS QDs is used for the imaging of live cells in different pH buffers and different cell lines. The FLIM images of AIS/ZnS QDs in live cells demonstrate different intracellular pH values in different regions, such as in lysosomes or cytoplasm. This method can also distinguish cancer cells from normal cells, and the fluorescence lifetime difference of the AIS/ZnS QDs between the two types of cells is 100 ± 7 ns. Most importantly, the exfoliated cervical cells from 20 patients are investigated using FLIM combined with AIS/ZnS QDs. The lifetime difference value between the normal and cervical cancer (CC) groups is 115 ± 9 ns, and the difference between the normal and the precancerous lesion group is 64 ± 9 ns. For the first time, the noninvasive method has been used for cervical cancer screening, and it has shown great improvement in sensitivity compared with a clinical conventional cytology examination.

Keywords

AIS/ZnS quantum dotsfluorescence lifetime imaging microscopyintracellular pH sensingcervical cancer screeningnoninvasive

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Nano Research
Volume 15 Issue 6,
June 2022
Pages 5193-5204
DOI: 10.1007/s12274-022-4104-1
Cite this article:
Su W, Yang D, Wang Y, et al. AgInS2/ZnS quantum dots for noninvasive cervical cancer screening with intracellular pH sensing using fluorescence lifetime imaging microscopy. Nano Research, 2022, 15(6): 5193-5204. https://doi.org/10.1007/s12274-022-4104-1
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Nano biology

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Received: 21 October 2021
Revised: 24 December 2021
Accepted: 27 December 2021
Published: 07 March 2022
© Tsinghua University Press 2022
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