Design and simulation of mRNA-9 interpreted in lung cancer using hydrogel platform

Authors

1 Biophysics Group, Faculty of Biological Science, Tehran, Iran

2 Biophysics group, Faculty of Biological Sciences, Tarbiat Modares University, Tehran-Iran

3 Dept of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran- Iran

Abstract
Cancer is one of the causes of death in human societies, and the main reason for failure in its treatment is late diagnosis and involvement of other body organs. Biomarkers measurement of body fluids can be one of the most important methods of cancer screening and diagnosis in the early stages. Circulating microRNAs have been proposed as new biomarkers for cancer diagnosis and prognosis. The use of these molecules, in addition to early and timely diagnosis before metastasis, will reduce the damage to the patient due to the possibility of non-invasive access. Therefore, developing a method to identify, reveal and quantify it is a necessity. In this study, a biosensor was designed to isolate and identify circulating blood microRNAs in a hydrogel platform. In our work, microRNA was isolated using a single-stranded DNA receptor probe and fixed in a platform containing hydrogels. By attaching the microRNA to the probe, the second probe, which complements the biotinylated DNA at the top of the microRNA, forms a sandwich structure. Finally, microRNA trapped between the two probes was detected by FITC-bound streptavidin in the hydrogel platform. In this research, different concentrations of microRNA-9 from 1000 picomolar to 1 femtomol were used to estimate the limit of detection (LOD) of the designed biosensor, and 50 femtomol was measured as the detection limit.

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1. Fakhri N, Abarghoei S, Dadmehr M, Hosseini M, Sabahi H, Ganjali MR. Paper based colorimetric detection of miRNA-21 using Ag/Pt nanoclusters. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2020;227:117529.
2. Choi C, Nam J-P, Nah J-W. Application of chitosan and chitosan derivatives as biomaterials. Journal of Industrial and Engineering Chemistry. 2016;33:1-10.
3. Zhao J, Fu W, Liao H, Dai L, Jiang Z, Pan Y, et al. The regulatory and predictive functions of miR-17 and miR-92 families on cisplatin resistance of non-small cell lung cancer. BMC cancer. 2015;15(1):1-14.
4. Lee D, Zhang W, Shirley SA, Kong X, Hellermann GR, Lockey RF, et al. Thiolated chitosan/DNA nanocomplexes exhibit enhanced and sustained gene delivery. Pharmaceutical research. 2007;24(1):157-67.
5. Zamay, T.N., et al. Current and prospective protein biomarkers of lung cancer. Cancers, 2017. 9(11): p. 155.
6. Liu X, Chen Y, Huang Q, He W, Feng Q, Yu B. A novel thermo-sensitive hydrogel based on thiolated chitosan/hydroxyapatite/beta-glycerophosphate. Carbohydrate Polymers. 2014;110:62-9.
7. Jantus-Lewintre, E., et al., Update on biomarkers for the detection of lung cancer. Lung Cancer: Targets and Therapy, 2012. 3: p. 21.
8. Akbuga J, Ozbas-Turan S, Ekentok C. Chitosan Nanoparticles in Gene Delivery. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Springer; 2016. p. 337-51.
9. Kritchenkov AS, Egorov AR, Artemjev AA, Kritchenkov IS, Volkova OV, Kurliuk AV, et al. Ultrasound-assisted catalyst-free thiol-yne click reaction in chitosan chemistry: Antibacterial and transfection activity of novel cationic chitosan derivatives and their based nanoparticles. International Journal of Biological Macromolecules. 2020;143:143-52.
10. Morin-Crini N, Lichtfouse E, Torri G, Crini G. Applications of chitosan in food, pharmaceuticals, medicine, cosmetics, agriculture, textiles, pulp and paper, biotechnology, and environmental chemistry. Environmental Chemistry Letters. 2019;17(4):1667-92.
11. Saeed RM, Dmour I, Taha MO. Stable chitosan-based nanoparticles using polyphosphoric acid or hexametaphosphate for tandem ionotropic/covalent crosslinking and subsequent investigation as novel vehicles for drug delivery. Frontiers in bioengineering and biotechnology. 2020;8:4.
12. Azmana M, Mahmood S, Hilles AR, Rahman A, Arifin MAB, Ahmed S. A review on chitosan and chitosan-based bionanocomposites: Promising material for combatting global issues and its applications. International journal of biological macromolecules. 2021;185:832-48.
13. Tekie FSM, Soleimani M, Zakerian A, Dinarvand M, Amini M, Dinarvand R, et al. Glutathione responsive chitosan-thiolated dextran conjugated miR-145 nanoparticles targeted with AS1411 aptamer for cancer treatment. Carbohydrate polymers. 2018;201:131-40.
14. Shaban NZ, Aboelsaad AM, Shoueir KR, Abdulmalek SA, Awad D, Shaban SY, et al. Chitosan-based dithiophenolato nanoparticles: Preparation, mechanistic information of DNA binding, antibacterial and cytotoxic activities. Journal of Molecular Liquids. 2020;318:114252.
15. Summonte S, Racaniello GF, Lopedota A, Denora N, Bernkop-Schnürch A. Thiolated polymeric hydrogels for biomedical application: Cross-linking mechanisms. Journal of Controlled Release. 2021;330:470-82.
16. Luo Q, Han Q, Wang Y, Zhang H, Fei Z, Wang Y. The thiolated chitosan: Synthesis, gelling and antibacterial capability. International Journal of Biological Macromolecules. 2019;139:521-30.
17. Shandilya R, Ranjan S, Khare S, Bhargava A, Goryacheva IY, Mishra PK. Point-of-care diagnostics approaches for detection of lung cancer-associated circulating miRNAs. Drug Discovery Today. 2021;26(6):1501-9.
18. Azzouz A, Hejji L, Kim K-H, Kukkar D, Souhail B, Bhardwaj N, et al. Advances in surface plasmon resonance–based biosensor technologies for cancer biomarker detection. Biosensors and Bioelectronics. 2022;197:113767.
19. Shafabakhsh R, Yousefi B, Asemi Z, Nikfar B, Mansournia MA, Hallajzadeh J. Chitosan: A compound for drug delivery system in gastric cancer-a review. Carbohydrate Polymers. 2020;242:116403.
20. Li W, Jiang C, Lu S, Wang F, Zhang Z, Wei T, et al. A hydrogel microsphere-based sensor for dual and highly selective detection of Al3+ and Hg2+. Sensors and Actuators B: Chemical. 2020;321:128490.
21. Kassahun G, Griveau S, Juillard S, Champavert J, Ringuede A, Bresson B, et al. Hydrogel matrix-grafted Impedimetric Aptasensors for the detection of Diclofenac. Langmuir. 2020;36(4):827-36.
22. Gam JJ, Babb J, Weiss R. A mixed antagonistic/synergistic miRNA repression model enables accurate predictions of multi-input miRNA sensor activity. Nature communications. 2018;9(1):1-12.
23. Chen W, Cai B, Geng Z, Chen F, Wang Z, Wang L, et al. Reducing false negatives in COVID-19 testing by using microneedle-based oropharyngeal swabs. Matter. 2020;3(5):1589-600.
24. Martínez-Ruvalcaba A, Chornet E, Rodrigue D. Viscoelastic properties of dispersed chitosan/xanthan hydrogels. Carbohydr Polym. 2017;67:586–595.
25. Da Som Jeon et al. Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015. Cancer Res Treat. 2023 Jan; 55(1): 103–111
26. Sahafnejad Z, Hashemzadeh H, Allahverdi A, Fathi A, Saievar-Iranizad E, Naderi-Manesh H. Sensitive detection of miR-9 in human serum: An electrochemical approach utilizing robust gold nanostructures for early diagnosis of lung cancer. Talanta Open. Vol 8. 100272-89
27. Smolarz B, Durczyński A, Romanowicz H, Szyłło K, Hogendorf P. miRNAs in Cancer (Review of Literature). Int J Mol Sci. 2022 Mar; 23(5): 2805
28. Shademan Behrouz et al. MicroRNAs as Targets for Cancer Diagnosis: Interests and Limitations. Adv Pharm Bull. 2023 Jul; 13(3): 435–445.