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Ultrabright silicon nanoparticle fluorescence probe for sensitive detection of cholesterol in human serum

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Abstract

A highly sensitive fluorescence-based assay for cholesterol detection was developed using water-dispersible green-emitting silicon nanoparticles (SiNPs) as a fluorescence indicator and enzyme-catalyzed oxidation product PPDox (Bandrowski’s base) as a quencher. The SiNPs were facilely synthesized via a simple, one-step hydrothermal treatment using 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethoxysilane (AEEA) as the silicon source, which has ultrahigh quantum yield and low phototoxicity. Under the catalysis of cholesterol oxidase (ChOx), hydrogen peroxide (H2O2) was generated as a result of cholesterol oxidation. Utilizing p-phenylenediamine (PPD) as the substrate for horseradish peroxidase (HRP) in the presence of H2O2 led to the production of PPDox. Based upon the inner filter effect (IFE), the established ultrasensitive fluorescent assay could accurately measure cholesterol. The limit of detection (LOD) of the assay was 0.018 μM with a linear range of 0.025–10 μM. The results for the detection of real serum samples by the proposed assay were comparable to those by a commercial reagent kit, demonstrating that our proposed strategy has high application potential in disease diagnosis and other related biological studies.

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References

  1. Maxfield FR, Tabas I. Role of cholesterol and lipid organization in disease. Nature. 2005;438(7068):612–21. https://doi.org/10.1038/nature04399.

    Article  CAS  PubMed  Google Scholar 

  2. Devadoss A, Burgess JD. Steady-state detection of cholesterol contained in the plasma membrane of a single cell using lipid bilayer-modified microelectrodes incorporating cholesterol oxidase. J Am Chem Soc. 2004;126(33):10214–5. https://doi.org/10.1021/ja047856e.

    Article  CAS  PubMed  Google Scholar 

  3. Amiri M, Arshi S. An overview on electrochemical determination of cholesterol. Electroanalysis. 2020;32(7):1391–407. https://doi.org/10.1002/elan.201900669.

    Article  CAS  Google Scholar 

  4. Sekretaryova AN, Beni V, Eriksson M, Karyakin AA, Turner AP, Vagin MY. Cholesterol self-powered biosensor. Anal Chem. 2014;86(19):9540–7. https://doi.org/10.1021/ac501699p.

    Article  CAS  PubMed  Google Scholar 

  5. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths (2007). The Lancet 370 (9602):1829–1839. https://doi.org/10.1016/s0140-6736(07)61778-4

  6. Huang S, Yang E, Yao J, Chu X, Liu Y, Zhang Y, Xiao Q. Nitrogen, cobalt co-doped fluorescent magnetic carbon dots as ratiometric fluorescent probes for cholesterol and uric acid in human blood serum. ACS Omega. 2019;4(5):9333–42. https://doi.org/10.1021/acsomega.9b00874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sinha A, Basiruddin S, Chakraborty A, Jana NR. beta-Cyclodextrin functionalized magnetic mesoporous silica colloid for cholesterol separation. ACS Appl Mater Interfaces. 2015;7(2):1340–7. https://doi.org/10.1021/am507817b.

    Article  CAS  PubMed  Google Scholar 

  8. Ronsein GE, Prado FM, Mansano FV, Oliveira MCB, Medeiros MHG, Miyamoto S, Di Mascio P. Detection and characterization of cholesterol-oxidized products using HPLC coupled to dopant assisted atmospheric pressure photoionization tandem mass spectrometry. Anal Chem. 2010;82(17):7293–301. https://doi.org/10.1021/ac1011987.

    Article  CAS  PubMed  Google Scholar 

  9. Houdová D, Soto J, Castro R, Rodrigues J, Soledad Pino-González M, Petković M, Bandosz TJ, Algarra M. Chemically heterogeneous carbon dots enhanced cholesterol detection by MALDI TOF mass spectrometry. J Colloid Interface Sci. 2021;591:373–83. https://doi.org/10.1016/j.jcis.2021.02.004.

    Article  CAS  PubMed  Google Scholar 

  10. Devadoss A, Burgess JD. Detection of cholesterol through electron transfer to cholesterol oxidase in electrode-supported lipid bilayer membranes. Langmuir. 2002;18(25):9617–21. https://doi.org/10.1021/la0258594.

    Article  CAS  Google Scholar 

  11. Dey RS, Raj CR. Development of an amperometric cholesterol biosensor based on graphene−Pt nanoparticle hybrid material. The Journal of Physical Chemistry C. 2010;114(49):21427–33. https://doi.org/10.1021/jp105895a.

    Article  CAS  Google Scholar 

  12. Zhao M, Li Y, Ma X, Xia M, Zhang Y. Adsorption of cholesterol oxidase and entrapment of horseradish peroxidase in metal-organic frameworks for the colorimetric biosensing of cholesterol. Talanta. 2019;200:293–9. https://doi.org/10.1016/j.talanta.2019.03.060.

    Article  CAS  PubMed  Google Scholar 

  13. Nirala NR, Pandey S, Bansal A, Singh VK, Mukherjee B, Saxena PS, Srivastava A. Different shades of cholesterol: gold nanoparticles supported on MoS2 nanoribbons for enhanced colorimetric sensing of free cholesterol. Biosens Bioelectron. 2015;74:207–13. https://doi.org/10.1016/j.bios.2015.06.043.

    Article  CAS  PubMed  Google Scholar 

  14. Kitchawengkul N, Prakobkij A, Anutrasakda W, Yodsin N, Jungsuttiwong S, Chunta S, Amatatongchai M, Jarujamrus P. Mimicking peroxidase-like activity of nitrogen-doped carbon dots (N-CDs) coupled with a laminated three-dimensional microfluidic paper-based analytical device (laminated 3D-muPAD) for smart sensing of total cholesterol from whole blood. Anal Chem. 2021;93(18):6989–99. https://doi.org/10.1021/acs.analchem.0c05459.

    Article  CAS  PubMed  Google Scholar 

  15. Maduraiveeran G, Sasidharan M, Ganesan V. Electrochemical sensor and biosensor platforms based on advanced nanomaterials for biological and biomedical applications. Biosens Bioelectron. 2018;103:113–29. https://doi.org/10.1016/j.bios.2017.12.031.

    Article  CAS  PubMed  Google Scholar 

  16. Thakur N, Kumar M, Das Adhikary S, Mandal D, Nagaiah TC. PVIM-Co5POM/MNC composite as a flexible electrode for the ultrasensitive and highly selective non-enzymatic electrochemical detection of cholesterol. Chem Commun (Camb). 2019;55(34):5021–4. https://doi.org/10.1039/c9cc01534e.

    Article  CAS  Google Scholar 

  17. Wu X, Chai Y, Yuan R, Zhong X, Zhang J. Synthesis of multiwall carbon nanotubes-graphene oxide-thionine-Au nanocomposites for electrochemiluminescence detection of cholesterol. Electrochim Acta. 2014;129:441–9. https://doi.org/10.1016/j.electacta.2014.02.103.

    Article  CAS  Google Scholar 

  18. Xu J, Jiang D, Qin Y, Xia J, Jiang D, Chen HY. C3N4 nanosheet modified microwell array with enhanced electrochemiluminescence for total analysis of cholesterol at single cells. Anal Chem. 2017;89(4):2216–20. https://doi.org/10.1021/acs.analchem.6b04635.

    Article  CAS  PubMed  Google Scholar 

  19. Mir IA, Kumar S, Bhat MA, Yuelin X, Wani AA, Zhu L (2021) Core@shell quantum dots as a fluorescent probe for the detection of cholesterol and heavy metal ions in aqueous media. Colloids and Surfaces A: Physicochemical and Engineering Aspects 626. https://doi.org/10.1016/j.colsurfa.2021.127090

  20. Li J, Liu T, Liu S, Li J, Huang G, Yang HH. Bifunctional magnetic nanoparticles for efficient cholesterol detection and elimination via host-guest chemistry in real samples. Biosens Bioelectron. 2018;120:137–43. https://doi.org/10.1016/j.bios.2018.08.046.

    Article  CAS  PubMed  Google Scholar 

  21. Han T, Zhu S, Wang S, Wang B, Zhang X, Wang G. Fluorometric methods for determination of H2O2, glucose and cholesterol by using MnO2 nanosheets modified with 5-carboxyfluorescein. Mikrochim Acta. 2019;186(5):269. https://doi.org/10.1007/s00604-019-3381-1.

    Article  CAS  PubMed  Google Scholar 

  22. Li D, Qiao Z, Yu Y, Tang J, He X, Shi H, Ye X, Lei Y, Wang K. In situ fluorescence activation of DNA-silver nanoclusters as a label-free and general strategy for cell nucleus imaging. Chem Commun (Camb). 2018;54(9):1089–92. https://doi.org/10.1039/c7cc08228b.

    Article  CAS  Google Scholar 

  23. Xu F, Shi H, He X, Wang K, He D, Guo Q, Qing Z, Yan L, Ye X, Li D, Tang J. Concatemeric dsDNA-templated copper nanoparticles strategy with improved sensitivity and stability based on rolling circle replication and its application in microRNA detection. Anal Chem. 2014;86(14):6976–82. https://doi.org/10.1021/ac500955r.

    Article  CAS  PubMed  Google Scholar 

  24. Ma C, Bian T, Yang S, Liu C, Zhang T, Yang J, Li Y, Li J, Yang R, Tan W. Fabrication of versatile cyclodextrin-functionalized upconversion luminescence nanoplatform for biomedical imaging. Anal Chem. 2014;86(13):6508–15. https://doi.org/10.1021/ac5010103.

    Article  CAS  PubMed  Google Scholar 

  25. Xia T, Liu G, Wang J, Hou S, Hou S. MXene-based enzymatic sensor for highly sensitive and selective detection of cholesterol. Biosens Bioelectron. 2021;183: 113243. https://doi.org/10.1016/j.bios.2021.113243.

    Article  CAS  PubMed  Google Scholar 

  26. Li Q, Luo TY, Zhou M, Abroshan H, Huang J, Kim HJ, Rosi NL, Shao Z, Jin R. Silicon nanoparticles with surface nitrogen: 90% quantum yield with narrow luminescence bandwidth and the ligand structure based energy law. ACS Nano. 2016;10(9):8385–93. https://doi.org/10.1021/acsnano.6b03113.

    Article  CAS  PubMed  Google Scholar 

  27. Phan LMT, Baek SH, Nguyen TP, Park KY, Ha S, Rafique R, Kailasa SK, Park TJ. Synthesis of fluorescent silicon quantum dots for ultra-rapid and selective sensing of Cr(VI) ion and biomonitoring of cancer cells. Mater Sci Eng C Mater Biol Appl. 2018;93:429–36. https://doi.org/10.1016/j.msec.2018.08.024.

    Article  CAS  PubMed  Google Scholar 

  28. Zhong Y, Sun X, Wang S, Peng F, Bao F, Su Y, Li Y, Lee S-T, He Y. Facile, large-quantity synthesis of stable, tunable-color silicon nanoparticles and their application for long-term cellular imaging. ACS Nano. 2015;9(6):5958–67. https://doi.org/10.1021/acsnano.5b00683.

    Article  CAS  PubMed  Google Scholar 

  29. Chen X, Zhang X, Xia L-Y, Wang H-Y, Chen Z, Wu F-G. One-step synthesis of ultrasmall and ultrabright organosilica nanodots with 100% photoluminescence quantum yield: long-term lysosome imaging in living, fixed, and permeabilized cells. Nano Lett. 2018;18(2):1159–67. https://doi.org/10.1021/acs.nanolett.7b04700.

    Article  CAS  PubMed  Google Scholar 

  30. Han Y, Chen Y, Feng J, Liu J, Ma S, Chen X. One-pot synthesis of fluorescent silicon nanoparticles for sensitive and selective determination of 2,4,6-trinitrophenol in aqueous solution. Anal Chem. 2017;89(5):3001–8. https://doi.org/10.1021/acs.analchem.6b04509.

    Article  CAS  PubMed  Google Scholar 

  31. Ma SD, Chen YL, Feng J, Liu JJ, Zuo XW, Chen XG. One-step synthesis of water-dispersible and biocompatible silicon nanoparticles for selective heparin sensing and cell imaging. Anal Chem. 2016;88(21):10474–81. https://doi.org/10.1021/acs.analchem.6b02448.

    Article  CAS  PubMed  Google Scholar 

  32. Geng X, Li Z, Hu Y, Liu H, Sun Y, Meng H, Wang Y, Qu L, Lin Y. One-pot green synthesis of ultrabright N-doped fluorescent silicon nanoparticles for cellular imaging by using ethylenediaminetetraacetic acid disodium salt as an effective reductant. ACS Appl Mater Interfaces. 2018;10(33):27979–86. https://doi.org/10.1021/acsami.8b09242.

    Article  CAS  PubMed  Google Scholar 

  33. Lillo CR, Romero JJ, Portolés ML, Diez RP, Caregnato P, Gonzalez MC. Organic coating of 1–2-nm-size silicon nanoparticles: effect on particle properties. Nano Res. 2015;8(6):2047–62. https://doi.org/10.1007/s12274-015-0716-z.

    Article  CAS  Google Scholar 

  34. Na M, Chen Y, Han Y, Ma S, Liu J, Chen X. Determination of potassium ferrocyanide in table salt and salted food using a water-soluble fluorescent silicon quantum dots. Food Chem. 2019;288:248–55. https://doi.org/10.1016/j.foodchem.2019.02.111.

    Article  CAS  PubMed  Google Scholar 

  35. Na M, Han Y, Chen Y, Ma S, Liu J, Chen X. Synthesis of silicon nanoparticles emitting yellow-green fluorescence for visualization of pH change and determination of intracellular pH of living cells. Anal Chem. 2021;93(12):5185–93. https://doi.org/10.1021/acs.analchem.0c05107.

    Article  CAS  PubMed  Google Scholar 

  36. Han Y, Chen Y, Feng J, Na M, Liu J, Ma Y, Ma S, Chen X. Investigation of nitrogen content effect in reducing agent to prepare wavelength controllable fluorescent silicon nanoparticles and its application in detection of 2-nitrophenol. Talanta. 2019;194:822–9. https://doi.org/10.1016/j.talanta.2018.11.008.

    Article  CAS  PubMed  Google Scholar 

  37. MacLachlan J, Wotherspoon ATL, Ansell RO, Brooks CJW. Cholesterol oxidase: sources, physical properties and analytical applications. J Steroid Biochem Mol Biol. 2000;72(5):169–95. https://doi.org/10.1016/S0960-0760(00)00044-3.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang Y, Schmid YRF, Luginbuhl S, Wang Q, Dittrich PS, Walde P. Spectrophotometric quantification of peroxidase with p-phenylenediamine for analyzing peroxidase-encapsulating lipid vesicles. Anal Chem. 2017;89(10):5484–93. https://doi.org/10.1021/acs.analchem.7b00423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Xiong J, He S, Wang Z, Xu Y, Zhang L, Zhang H, Jiang H. Dual-readout fluorescence quenching immunochromatographic test strips for highly sensitive simultaneous detection of chloramphenicol and amantadine based on gold nanoparticle-triggered photoluminescent nanoswitch control. J Hazard Mater. 2022;429: 128316. https://doi.org/10.1016/j.jhazmat.2022.128316.

    Article  CAS  PubMed  Google Scholar 

  40. Zhang J, Zhou R, Tang D, Hou X, Wu P. Optically-active nanocrystals for inner filter effect-based fluorescence sensing: achieving better spectral overlap. TrAC, Trends Anal Chem. 2019;110:183–90. https://doi.org/10.1016/j.trac.2018.11.002.

    Article  CAS  Google Scholar 

  41. Ni P, Chen C, Jiang Y, Zhang C, Wang B, Lu Y, Wang H (2020) A fluorescent assay for alkaline phosphatase activity based on inner filter effect by in-situ formation of fluorescent azamonardine. Sensors and Actuators B: Chemical 302. https://doi.org/10.1016/j.snb.2019.127145

  42. Mu X, Wu M, Zhang B, Liu X, Xu S, Huang Y, Wang X, Song D, Ma P, Sun Y (2021) A sensitive “off-on” carbon dots-Ag nanoparticles fluorescent probe for cysteamine detection via the inner filter effect. Talanta 221. https://doi.org/10.1016/j.talanta.2020.121463

  43. Wang HB, Tao BB, Wu NN, Zhang HD, Liu YM. Glutathione-stabilized copper nanoclusters mediated-inner filter effect for sensitive and selective determination of p-nitrophenol and alkaline phosphatase activity. Spectrochim Acta A Mol Biomol Spectrosc. 2022;271: 120948. https://doi.org/10.1016/j.saa.2022.120948.

    Article  CAS  PubMed  Google Scholar 

  44. Zhang J, Lu X, Lei Y, Hou X, Wu P. Exploring the tunable excitation of QDs to maximize the overlap with the absorber for inner filter effect-based phosphorescence sensing of alkaline phosphatase. Nanoscale. 2017;9(40):15606–11. https://doi.org/10.1039/c7nr03673f.

    Article  CAS  PubMed  Google Scholar 

  45. Chang HC, Ho JA. Gold nanocluster-assisted fluorescent detection for hydrogen peroxide and cholesterol based on the inner filter effect of gold nanoparticles. Anal Chem. 2015;87(20):10362–7. https://doi.org/10.1021/acs.analchem.5b02452.

    Article  CAS  PubMed  Google Scholar 

  46. Chen Y, Yang G, Gao S, Zhang L, Yu M, Song C, Lu Y. Highly rapid and non-enzymatic detection of cholesterol based on carbon nitride quantum dots as fluorescent nanoprobes. RSC Adv. 2020;10(65):39596–600. https://doi.org/10.1039/d0ra07495k.

    Article  CAS  Google Scholar 

  47. Su Q, Gan L, Zhu Y, Yang X (2021) Dual-emissive fluorescence and phosphorescence detection of cholesterol and glucose based on carbon dots-cyanuric acid complex quenched by MnO2 nanosheets. Sensors and Actuators B: Chemical 335. https://doi.org/10.1016/j.snb.2021.129715

  48. Hassanzadeh J, Khataee A, Eskandari H. Encapsulated cholesterol oxidase in metal-organic framework and biomimetic Ag nanocluster decorated MoS2 nanosheets for sensitive detection of cholesterol. Sens Actuators, B Chem. 2018;259:402–10. https://doi.org/10.1016/j.snb.2017.12.068.

    Article  CAS  Google Scholar 

  49. Zhao L, Wu Z, Liu G, Lu H, Gao Y, Liu F, Wang C, Cui J, Lu G. High-activity Mo, S co-doped carbon quantum dot nanozyme-based cascade colorimetric biosensor for sensitive detection of cholesterol. J Mater Chem B. 2019;7(44):7042–51. https://doi.org/10.1039/c9tb01731c.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 22074052 and 22004046).

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Authors and Affiliations

  1. Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, College of Chemistry, Jilin University, Qianjin Street 2699, Changchun, 130012, China

    Xiwen Ye, Xiaowei Mu, Ying Sun, Pinyi Ma & Daqian Song

  2. School of Marine Science and Technology, Harbin Institute of Technology at Weihai, Weihai, 264209, Shandong, China

    Yanxiao Jiang

  3. Department of Thoracic Surgery, The First Hospital of Jilin University, Xinmin Street 71, Changchun, 130021, China

    Ping Ren

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  1. Xiwen Ye
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Ye, X., Jiang, Y., Mu, X. et al. Ultrabright silicon nanoparticle fluorescence probe for sensitive detection of cholesterol in human serum. Anal Bioanal Chem 414, 3827–3836 (2022). https://doi.org/10.1007/s00216-022-04024-4

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