Detection of Endocrine Disrupting Drugs with Quantum Dot Molecularly Imprinted Polymer

Abstract

Endocrine disrupting chemicals are causing serious harm to health and increasing the disease burden worldwide and pose a global health risk by disrupting the endocrine system through various biological pathways. The combination of MIPs and QDs offers high sensitivity fluorescence analysis and holds promise for detection at very low concentrations. In recent years, quantum dots have found significant application in biomedical applications such as biosensors and clinical diagnosis due to their traceable optical properties. QDs have unique optical advantages such as high luminescence intensity, high molar extinction coefficient and customizable emission properties depending on their size. With the help of MIPs, QDs specifically recognize target analytes, interact with the fluorescent signal source and thus changes in the fluorescence intensity of the target analyte can be monitored. The presence of endocrine disrupting drugs in water, biological fluids, animal feed and meat samples is known as a result of studies. Considering the difficulty and durability of biodegradation of these drugs, their detection by QD/MIPs is of great importance. This review summarizes recent work on the development of fluorescent QD/MIP sensors for the detection of endocrine disrupting drugs.

Keywords

• endocrine disrupting drugs
• quantum dots
• molecular imprinted polymers
• fluorescence

References

1. 1. Son E, Kwon KH. How body burden from exposure to endocrine disruptors effects accelerated aging?. Environ Res Tec. 2023;6(4):383-390. https://doi.org/10.35208/ert.1334434
2. 2. Sabir S, Akhtar MF, Saleem A. Endocrine disruption as an adverse effect of non-endocrine targeting pharmaceuticals. Envıron Scı Pollut R. 2019;26:1277–1286. https://doi.org/10.1007/s11356-018-3774-4
3. 3. Mostafalou S, Abdollahi M. Pesticides and human chronic diseases: evidences, mechanisms and perspectives. Toxicol Appl Pharm. 2013;268(2):157–177. https://doi.org/10.1016/j.taap.2013.01.025
4. 4. Perng W, Cantoral A, Soria-Contreras D, Betanzos-Robledo L, Kordas K, Liu Y, et al. Exposure to obesogenic endocrine disrupting chemicals and obesity among youth of Latino or Hispanic origin in the United States and Latin America: A lifecourse perspective. Obes. Rev. 2021;22(S3). https://doi.org/10.1111/obr.13245
5. 5. Güntürk A. Güncel Obezojenler. In: Kadiroğlu A.K, editor. Güncel Genel Dahiliye Çalışmaları. Chapter 4. 2022. p. 35-47.
6. 6. Rato L, Sousa AC. The impact of endocrine-disrupting chemicals in male fertility: focus on the action of obesogens. J. Xenobiotics, 2021;11(4):163-196. https://doi.org/10.3390/jox11040012
7. 7. Mascarenhas C, Sousa ACA, Rato L. Effects of Pharmaceutical Substances with Obesogenic Activity on Male Reproducti-ve Health. Int. J. Mol. Sci. Int. J. Mol. Sci. 2024; 25(4). https://doi.org/10.3390/ijms25042324
8. 8. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. New Eng. J. Med. 2006;355:2427–2443. doi: 10.1056/NEJMoa066224

9. 9. Messerli FH, Bell DSH, Fonseca V, Katholi RE, McGill JB, Phillips RA, et al. Body weight changes with β-blocker use: Results from GEMINI. Am. J. Med. 2007;120(7): 610-615. doi:10.1016/j.amjmed.2006.10.017
10. 10. Verhaegen AA, Van Gaal LF. Drug-induced obesity and its metabolic consequences: A review with a focus on mechanisms and possible therapeutic options. J. Endocrinol. Investig. 2017;40(11):1165–1174. https://doi.org/10.1007/s40618-017-0719-6
11. 11. Spertus J, Horvitz-Lennon M, Abing H, Normand SL. Risk of weight gain for specific antipsychotic drugs. A meta-analysis. NPJ Schizophr. 2018;4:12. doi:10.1038/s41537-018-0053-9
12. 12. Verrotti A, D’Egidio C, Mohn A, Coppola G, Chiarelli F. Weight gain following treatment with valproic acid: Pathogenetic mechanisms and clinical implications. Obes. Rev. 2011;12(5):e32–e43. https://doi.org/10.1111/j.1467-789X.2010.00800.x
13. 13. Alonso-Magdalena P, Ropero AB, Carrera MP, Cederroth CR, Baquié M. Pancreatic Insulin Content Regulation by the Estrogen Receptor. Endocrine disruptors and the fetal origin of diseases, PLoS ONE. 2008;3(4). https://doi.org/10.1371/journal.pone.0002069
14. 14. Kristensen DM, Skalkam ML, Audouze K, Lesne L, Desdo-its-Lethimonier C, Frederiksen H, et al. Many putative endocrine disruptors ınhibit prostaglandin synthesis. Envıron Health Persp. 2011;119(4):534-541. https://doi.org/10.1289/ehp.1002635
15. 15. Iyer, P., Abadilla K, Dobs A. Substances of abuse and their hormonal effects. In: el-Guebaly N, Carra G, Galanter M, editors. Textbook of addiction treatment: International Perspectives, Springer, Milano; 2015.p.1811-1831. https://doi.org/10.1007/978-88-470-5322-9_160
16. 16. Iguchi T, Watanabe H, Katsu Y. Application of ecotoxicogenomics for studying endocrine disruption in vertebrates and in-vertebrates. Envıron Health Persp. 2006;114:101–105. https://doi.org/10.1289/ehp.8061
17. 17. Wang YF, Pan MM, Yu X, Xu L. The recent advances of fluorescent sensors based on molecularly ımprinted fluorescent nanoparticles for pharmaceutical analysis Curr. Med. Sci. 2020;40(3) 407–421. https://doi.org/10.1007/s11596-020-2195-z
18. 18. Sajini T, Mathew B. A brief overview of molecularly imprinted polymers: Highlighting computational design, nano and photo-responsive imprinting. Talanta Open. 2021;4. https://doi.org/10.1016/j.talo.2021.100072
19. 19. Poole CF, Poole SK. Principles and practice of solid-phase extraction. In: D. Barcelo, editor. Sampling and Sample Preparation for Field and Laboratory. Chapter 12. 37. Compr. Anal. Chem. Elsevier; 2002. p. 341-387 https://doi.org/10.1016/B978-0-12-381373-2.00041-7
20. 20. Bahrania S, Aslanib R, Hashemic R, Mousavid S, Ghaedia M. Introduction to molecularly imprinted polymer. In: Hubbard AT, editor. Interface Science and Technology. Chapter 7. 33. Elsevıer; 2021. p. 511-556 https://doi.org/10.1016/B978-0-12-818805-7.00006-0
21. 21. Altammar K. A review on nanoparticles: characteristics, synthesis, applications, and challenges. Front Microbiol. 2023;14. https://doi.org/10.3389/fmicb.2023.1155622
22. 22. Bangal M, Ashtaputre S, Marathe S, Ethıraj A, Hebalkar N, Gosavı SW, et al. Semiconductor nanoparticles. Hyperfine Interact. 2005;160:81-84 https://doi.org/10.1007/s10751-005-9151-y
23. 23. Cotta MA. Quantum Dots and Their Applications: What Lies Ahead?. ACS Apply. Nano Mater. 2020;3(6):4920-4924 https://doi.org/10.1021/acsanm.0c01386
24. 24. Agarwal K, Rai H, Mondal S. Quantum dots: An overview of synthesis, properties, and applications. Mater. Res. Express. 2023;10(6). https://doi.org/10.1088/2053-1591/acda17
25. 25. Martin-Esteban A. Molecularly-imprinted polymers as a versatile, highly selective tool in sample preparation. TrAC Trends Anal. Chem. 2013;45:169–181. doi: 10.1016/j.trac.2012.09.023.
26. 26. Pan J, Chen W, Ma Y, Pan G. Molecularly imprinted polymers as receptor mimics for selective cell recognition. Chem Soc Rev. 2018;47(15):5574–5587. https://doi.org/10.1039/c7cs00854f
27. 27. Wulff G, Vietmeier J. Enzyme-analogue built polymers, 26. Enantioselective synthesis of amino acids using polymers possessing chiral cavities obtained by an imprinting procedure with template molecules. Die Makromol Chem 1989;190(7):1727–1735. https://doi.org/10.1002/macp.1989.021900724
28. 28. Wulff G, Wolf G. Zur Chemie von Haftgruppen, VI. Über die Eignung verschiedener Aldehyde und Ketone als Haftgruppen für Monoalkohole. Chem Ber. 1986;119(6):1876–1889. https://doi.org/10.1002/cber.19861190610
29. 29. Shea KJ, Dougherty TK. Molecular recognition on synthetic amorphous surfaces. the influence of functional group positioning on the effectiveness of molecular recognition. J Am Chem Soc. 1986;108:1091–1093. https://doi.org/10.1021/ja00265a046
30. 30. Wulff G, Schauhoff S. Enzyme-analog-built polymers. 27. Racemic resolution of free sugars with macroporous polymers prepared by molecular imprinting. Selectivity dependence on the arrangement of functional groups versus spatial requirements. J Org Chem. 1991;56(1):395–400. https://doi.org/10.1021/jo00001a071
31. 31. Hashim SNNS, Boysen RI, Schwarz LJ, Danylec B, Hearn MTW. A comparison of covalent and non-covalent imprinting strategies for the synthesis of stigmasterol imprinted polymers. J Chromatogr A. 2014; 1359: 35-43. https://doi.org/10.1016/j.chroma.2014.07.034
32. 32. Takeuchi T, Matsui J. Molecular imprinting: an approach to “ tailor-made ” synthetic polymers with biomimetic functi-ons. Acta Polym. 1996; 47: 471-480. https://doi.org/10.1002/actp.1996.010471101
33. 33. Whitcombe MJ, Rodriguez ME, Villar P, Vulfson EN. A new method for the Introduction of recognition site functionality into polymers prepared by molecular imprinting: synthesis and characterization of polymeric receptors for cholesterol. J Am Chem Soc. 1995;117(27): 7105-7111. https://doi.org/10.1021/ ja00132a01034.
34. 34. Farooq S, Nie J, Cheng Y, Yan Z, Li J, Bacha SA. Molecularly imprinted polymers’ application in pesticide residue detection. Analyst. 2018;143(17):3971–3989. https://doi.org/10.1039/c8an00907d
35. 35. Sajini T, Mathew B. A brief overview of molecularly imprinted polymers: Highlighting computational design, nano and photo-responsive imprinting. Talanta Open. 2021;4:100072. https://doi.org/10.1016/j.talo.2021.100072
36. 36. Yang Y, Shen X. Preparation and application of molecularly imprinted polymers for flavonoids: Review and perspective. Molecules. 2022;27(21):7355. https://doi.org/10.3390/molecules27217355
37. 37. Metwally MG, Benhawy AH, Khalifa RM, El Nashar RM, Trojanowicz M. Application of molecularly imprinted polymers in the analysis of waters and wastewaters. Molecules. 2021;26(21):6515. ttps://doi.org/10.3390/molecules26216515
38. 38. Yang K, Berg MM, Zhao C, Ye L. One-Pot synthesis of hydrophilic molecularly imprinted nanoparticles. Macromolecules. 2009;42(22):8739–8746. https://doi.org/10.1021/ma901761z
39. 39. Hungenberg K.D, Jahns E. Trends in emulsion polymerization processes from an industrial perspective. Adv. Polym. Sci. 2017;280:195–214. https://doi.org/10.1007/12_2017_14
40. 40. Zuo J, Ma P, Li Z, Zhang Y, Xiao D, Wu H, et al. Application of molecularly imprinted polymers in plant natural products: Current progress and future perspectives. Macromol Mater Eng. 2023;308(3):2200499. https://doi.org/10.1002/mame.202200499
41. 41. Zare EN, Fallah Z, Le VT, Doan VD, Mudhoo A, Joo SW, et al. Remediation of pharmaceuticals from contaminated water by molecularly imprinted polymers: a review. Environ Chem Let. 2022;20(4):2629-2664. https://doi.org/10.1007/s10311-022-01439-4
42. 42. Bokov D, Turki Jalil A, Chupradit S, Suksatan W, Javed Ansari M, Shewael I. H. Nanomaterial by sol-gel method: synthesis and application. Advances in materials science and engineering, 2021;2021(1). https://doi.org/10.1155/2021/5102014
43. 43. Włoch M, Datta J. Synthesis and polymerisation techniques of molecularly imprinted polymers. In: D Barceló, editör. Mip Synthesis, Characteristics and Analytical Application. 86. Compr. Anal. Chem. 2019;86:17-40. https://doi.org/10.1016/bs.coac.2019.05.011
44. 44. de Aquino SF, Brandt EMF, Bottrel SEC, Gomes FBR, Silva SDQ. Occurrence of pharmaceuticals and endocrine disrupting compounds in Brazilian water and the risks they may represent to human health. J. Environ. Public Health. 2021;18(22):11765. https://doi.org/10.3390/ijerph182211765
45. 45. Albert O, Desdoits-Lethimonier C, Lesné L, Legrand A, Guillé F, Bensalah K. Paracetamol, aspirin and indomethacin display endocrine disrupting properties in the adult human testis in vitro. Hum Reprod. 2013;28(7):1890-1898. doi:10.1093/humrep/det112
46. 46. Mendonça LL, Khamashta MA, Nelson-Piercy C, Hunt BJ, Hughes GRV. Non-steroidal anti-inflammatory drugs as a possible cause for reversible infertility. Rheumatology. 2000;39(8):880-882. doi:10.1093/romatoloji/39.8.880
47. 47. Montaseri H, Forbes P. Molecularly imprinted polymer coated quantum dots for fluorescence sensing of acetaminophen. Mater. Today Commun. 2018;17:480-492. https://doi.org/10.1016/j.mtcomm.2018.10.007
48. 48. Li K, Zhang M, Ye X, Zhang Y, Li G, Fu R, et al. Highly sensitive and selective detection of naproxen via molecularly imprinted carbon dots as a fluorescent sensor. RSC Adv. 2021;11(46):29073-29079. https://doi.org/10.1039/D1RA04817A
49. 49. Dehghani Z, Akhond M, Absalan G. Carbon quantum dots embedded silica molecular imprinted polymer as a novel and sensitive fluorescent nanoprobe for reproducible enantioselective quantification of naproxen enantiomers. Microchem. J. 2021;160:105723. https://doi.org/10.1016/j.mic-roc.2020.105723
50. 50. Chen S, Zhou S, Fu J, Tang S, Wu X, Zhao P, et al. A near infrared fluorescence imprinted sensor based on zinc oxide nanorods for rapid determination of ketoprofen. Analytical Methods. 2021;13(25):2836-2846. https://doi.org/10.1039/D1AY00555C
51. 51. Bhogal S, Kaur K, Maheshwari S, Malik AK. Surface molecularly imprinted carbon dots based core-shell material for selective fluorescence sensing of ketoprofen. J Fluoresc. 2019;29:145-154. https://doi.org/10.1007/s10895-018-2322-4
52. 52. Wei X, Zhou Z, Hao T, Xu Y, Li H, Lu K. et al. Specific recognition and fluorescent determination of aspirin by using core-shell CdTe quantum dot-imprinted polymers Microchim Acta. 2015;182:1527–1534. https://doi.org/10.1007/s00604-015-1463-2
53. 53. Tawfika S, Huya B, Sharipova M, Al Abd-Elaal A, Leea Y. Enhanced fluorescence of CdTe quantum dots capped with a novel nonionic alginate for selective optosensing of ibuprofen. Sensor Actuat B-Chem. 2018;256:243-250. https://doi.org/10.1016/j.snb.2017.10.092
54. 54. Sohrabi N, Amini-Fazl M, Mohammadi R. Adsorption and detection tramadol in aqueous solution by fluorescentmagnetic molecularly imprinting polymers. J. Taiwan Inst. Chem. 2024;155:105314. https://doi.org/10.1016/j.jtice.2023.105314
55. 55. Reynolds GP, Kirk SL. Metabolic side effects of antipsychotic drug treatment–pharmacological mechanisms. Pharmacol Therapeut. 2010;125(1):169-179. https://doi.org/10.1016/j.pharmthera.2009.10.010
56. 56. Khalil RB, Richa S. Thyroid adverse effects of psychotropic drugs: a review. Clın Neuropharmacol. 2011;34(6):248-255. doı: 10.1097/WNF.0b013e31823429a7
57. 57. Ensafi A, Zakery M, Rezaei B. An optical sensor with specific binding sites for the detection of thioridazine hydrochloride based on ZnO-QDs coated with molecularly imprinted polymer. Spectrochım Acta A. 2019;206:460-465. https://doi.org/10.1016/j.saa.2018.08.040
58. 58. Dalkilic EB. Effects of antiepileptic drugs on hormones. Neuroscı Lett. 2021;754:135800. https://doi.org/10.1016/j.neulet.2021.135800
59. 59. Shariati R, Rezaei B, Jamei HR, Ensafi A. Application of coated green source carbon dots with silica molecularly imprinted polymers as a fluorescence probe for selective and sensitive determination of phenobarbital. Talanta. 2019;194:143–149. https://doi.org/10.1016/j.talanta.2018.09.069
60. 60. Onslev J, Fiorenza M, Thomassen M, Havelund J, Bangsbo J, Færgeman N. Beta 2-agonist impairs muscle insulin sensitivity in persons with insulin resistance. J Clın Endocr Metab. 2025;110(1):275-288. doi: 10.1210/clinem/dgae381
61. 61. Raksawong P, Chullasat K, Nurerk P, Kanatharana P, Davis F, Bunkoed O. A hybrid molecularly imprinted polymer coated quantum dot nanocomposite optosensor for highly sensitive and selective determination of salbutamol in animal feeds and meat samples. Anal Bioanal Chem. 2017;409:4697–4707. https://doi.org/10.1007/s00216-017-0466-8
62. 62. Brass EP. Effects of antihypertensive drugs on endocrine function. Drugs. 1984;27(5):447-458. doi: 10.2165/00003495-198427050-00004
63. 63. Jalili R, Amjadi M. Surface molecular imprinting on silane functionalized carbon dots for selective recognition of nifedipine. RSC Adv. 2015;5:90. https://doi.org/10.1039/C5RA12189B
64. 64. Ensafi A, Kazemifard N, Rezaei B. Development of a nano plastic antibody for determination of propranolol using CdTe quantum dots. Sensor Actuat B-Chem. 2017;252:846-853. https://doi.org/10.1016/j.snb.2017.06.078
65. 65. Mondillo C, Varela ML, Abiuso AMB, Vázquez R. Potential negative effects of anti-histamines on male reproductive function. Reproduction. 2018;155(5):R221-R227. https://doi.org/10.1530/REP-17-0685.
66. 66. Cui Y, Su A, Feng J, Dong W, Li J, Wang H. Development of silica molecularly imprinted polymer on carbon dots as a fluorescence probe for selective and sensitive determination of cetirizine in saliva and urine. Spectrochım Acta A. 2022;264. https://doi.org/10.1016/j.saa.2021.120293
67. 67. Ensafi A, Zakery M, Rezaei B. Synthesis of molecularly imprinted polymer on carbon quantum dots as an optical sensor for selective fluorescent determination of promethazine hydrochloride. Sensor Actuat B-Chem. 2018;257:889-896. https://doi.org/10.1016/j.snb.2017.11.050
68. 68. Kadowaki T, Hagura R, Kajinuma H, Kuzuya N, Yoshida S. Chlorpropamide-induced hyponatremia: incidence and risk factors. Diabetes Care. 1983;6:468–71. doi: 10.2337/diaca-re.6.5.468
69. 69. Gazizadeh M, Dehghan G, Soleymani J. A dual-emission ratiometric fluorescent biosensor for ultrasensitive detection of glibenclamide using S-CDs/CdS quantum dots. Spectrochım Acta A. 2023;297:122714. https://doi.org/10.1016/j.saa.2023.122714