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Investigating Efficacy of Three DNA-Aptamers in Targeted Plasmid Delivery to Human Prostate Cancer Cell Lines

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Abstract

Selection of targeted and efficient carriers to deliver drugs and genes to cells and tissues is still a major challenge and to overcome this obstacle, aptamers conjugated to nanoparticles have been broadly examined. To assess whether polycation of aptamers can improve plasmid delivery efficacy, we investigated the effect of three DNA-aptamers (AS1411, WY-5a, and Sgs-8) conjugated to branched polyethylenimine (b-PEI; MW ∼25 kDa) with different combinations of gene (plasmid) for delivery to prostate cancer cell lines (DU145 and PC3). According to transfection assessments, the dual conjugation of aptamers (AS:WY) with b-PEI produced the best results and increased the efficiency of plasmid delivery to up to three folds compared to unmodified PEI. Surprisingly, triple aptamer arrangement not only reduced transfection ability but also showed cytotoxicity. While our results demonstrated potential synergistic effects of AS1411 and WY-5a aptamers for gene delivery, it is important to note that the present evidence relies on the aptamer and cell types.

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References

  1. Khazaei, Z., Sohrabivafa, M., Momenabadi, V., Moayed, L., & Goodarzi, E. (2019). Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide prostate cancers and their relationship with the human development index. Advances in Human Biology, 9, 245–250.

    Google Scholar 

  2. Mattia, G., Puglisi, R., Ascione, B., Malorni, W., Carè, A., & Matarrese, P. (2018). Cell death-based treatments of melanoma:Conventional treatments and new therapeutic strategies. Cell Death & Disease, 9, 112–112.

    Google Scholar 

  3. Alavi, S. J., Gholami, L., Askarian, S., Darroudi, M., Massoudi, A., Rezaee, M., & Oskuee, R. K. (2017). Hyperbranched–dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly (propyleneimine) dendrimers: Synthesis, characterization, and evaluation of transfection efficiency. Journal of Nanoparticle Research, 19, 49.

    Google Scholar 

  4. Glinka, E. M. (2012). Eukaryotic expression vectors bearing genes encoding cytotoxic proteins for cancer gene therapy. Plasmid, 68, 69–85.

    CAS  Google Scholar 

  5. Wang, W., Li, W., Ma, N., & Steinhoff, G. (2013). Non-viral gene delivery methods. Current Pharmaceutical Biotechnology, 14, 46–60.

    CAS  Google Scholar 

  6. Hashemi, M., Tabatabai, S. M., Parhiz, H., Milanizadeh, S., Farzad, S. A., Abnous, K., & Ramezani, M. (2016). Gene delivery efficiency and cytotoxicity of heterocyclic amine-modified PAMAM and PPI dendrimers. Materials Science and Engineering C, 61, 791–800.

    CAS  Google Scholar 

  7. Ebrahimian, M., Taghavi, S., Mokhtarzadeh, A., Ramezani, M., & Hashemi, M. (2017). Co-delivery of doxorubicin encapsulated PLGA nanoparticles and Bcl-xL shRNA using alkyl-modified PEI into breast cancer cells. Applied Biochemistry and Biotechnology, 183, 126–136.

    CAS  Google Scholar 

  8. Askarian, S., Abnous, K., Darroudi, M., Oskuee, R. K., & Ramezani, M. (2016). Gene delivery to neuroblastoma cells by poly (l-lysine)-grafted low molecular weight polyethylenimine copolymers. Biologicals, 44, 212–218.

    CAS  Google Scholar 

  9. Cho, T. J., Gorham, J. M., Pettibone, J. M., Liu, J., Tan, J., & Hackley, V. A. (2019). Parallel multi-parameter study of PEI-functionalized gold nanoparticle synthesis for bio-medical applications: Part 1—a critical assessment of methodology, properties, and stability. Journal of Nanoparticle Research, 21, 188.

    Google Scholar 

  10. Kumar, K., Vulugundam, G., Jaiswal, P. K., Shyamlal, B. R. K., & Chaudhary, S. (2017). Efficacious cellular codelivery of doxorubicin and EGFP siRNA mediated by the composition of PLGA and PEI protected gold nanoparticles. Bioorganic & Medicinal Chemistry Letters, 27, 4288–4293.

    CAS  Google Scholar 

  11. Uğurlu, Ö., Barlas, F. B., Evran, S., & Timur, S. (2020). The cell-penetrating YopM protein-functionalized quantum dot-plasmid DNA conjugate as a novel gene delivery vector. Plasmid, 110, 102513.

    Google Scholar 

  12. Chen, J., Wang, K., Wu, J., Tian, H., & Chen, X. (2018). Polycations for gene delivery: Dilemmas and solutions. Bioconjugate Chemistry, 30, 338–349.

    Google Scholar 

  13. Abnous, K., Danesh, N. M., Ramezani, M., Lavaee, P., Jalalian, S. H., Yazdian-Robati, R., Emrani, A. S., Hassanabad, K. Y., & Taghdisi, S. M. (2017). A novel aptamer-based DNA diamond nanostructure for in vivo targeted delivery of epirubicin to cancer cells. RSC Advances, 7, 15181–15188.

    CAS  Google Scholar 

  14. Wyatt, L. C., Moshnikova, A., Crawford, T., Engelman, D. M., Andreev, O. A., & Reshetnyak, Y. K. (2018). Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors. Proceedings of the National Academy of Sciences, 115, E2811–E2818.

    CAS  Google Scholar 

  15. Oroojalian, F., Rezayan, A. H., Shier, W. T., Abnous, K., & Ramezani, M. (2017). Megalin-targeted enhanced transfection efficiency in cultured human HK-2 renal tubular proximal cells using aminoglycoside-carboxyalkyl-polyethylenimine-containing nanoplexes. International Journal of Pharmaceutics, 523, 102–120.

    CAS  Google Scholar 

  16. Noh, Y., Kim, M.-J., Mun, H., Jo, E.-J., Lee, H., & Kim, M.-G. (2019). Aptamer-based selective KB cell killing by the photothermal effect of gold nanorods. J Nanoparticle Res, 21, 112.

    Google Scholar 

  17. Zhang, W.-Y., Chen, H.-L., & Chen, Q.-C. (2019). In vitro selection of aptamer S1 against MCF-7 human breast cancer cells. Bioorganic & Medicinal Chemistry Letters, 29, 2393–2397.

    CAS  Google Scholar 

  18. Ameri, M., Eskandari, S., & Nezafat, N. (2021). An overview of aptamer: The prominent applications and different computational tools for its design. Current Pharmaceutical Biotechnology, 22, 1273–1286.

    CAS  Google Scholar 

  19. Wang, T., Chen, C., Larcher, L., Barrero, R. A., & Veedu, R. N. (2018). Three decades of nucleic acid aptamer technologies: Lessons learned, progress and opportunities on aptamer development. Biotechnology Advances, 37, 28–50.

    Google Scholar 

  20. Ding, F., Gao, Y., & He, X. (2017). Recent progresses in biomedical applications of aptamer-functionalized systems. Bioorganic & Medicinal Chemistry Letters, 27, 4256–4269.

    CAS  Google Scholar 

  21. Miranda, A., Santos, T., Carvalho, J., Alexandre, D., Jardim, A., Caneira, C. F., Vaz, V., Pereira, B., Godinho, R., & Brito, D. (2021). Aptamer-based approaches to detect nucleolin in prostate cancer. Talanta, 226, 122037.

    CAS  Google Scholar 

  22. Sylvester, P. W. (2011). Optimization of the tetrazolium dye (MTT) colorimetric assay for cellular growth and viability. In Drug design and discovery (pp. 157–168). Humana Press.

    Google Scholar 

  23. Zarei, H., Kazemi Oskuee, R., Hanafi-Bojd, M. Y., Gholami, L., Ansari, L., & Malaekeh-Nikouei, B. (2019). Enhanced gene delivery by polyethyleneimine coated mesoporous silica nanoparticles. Pharmaceutical Development and Technology, 24, 127–132.

    CAS  Google Scholar 

  24. Wang, Y., Deng, W., Li, N., Neri, S., Sharma, A., Jiang, W., & Lin, S. H. (2018). Combining immunotherapy and radiotherapy for cancer treatment: Current challenges and future directions. Frontiers in Pharmacology, 9, 185.

    Google Scholar 

  25. Li, L., Xu, S., Yan, H., Li, X., Yazd, H. S., Li, X., Huang, T., Cui, C., Jiang, J., & Tan, W. (2021). Nucleic acid aptamers for molecular diagnostics and therapeutics: Advances and perspectives. Angewandte Chemie International Edition, 60, 2221–2231.

    CAS  Google Scholar 

  26. Ng, E. W., Shima, D. T., Calias, P., Cunningham, E. T., Guyer, D. R., & Adamis, A. P. (2006). Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nature Reviews Drug Discovery, 5, 123–132.

    CAS  Google Scholar 

  27. Baneshi, M., Dadfarnia, S., Shabani, A. M. H., Sabbagh, S. K., Haghgoo, S., & Bardania, H. (2019). A novel theranostic system of AS1411 aptamer-functionalized albumin nanoparticles loaded on iron oxide and gold nanoparticles for doxorubicin delivery. International Journal of Pharmaceutics, 564, 145–152.

    CAS  Google Scholar 

  28. Walia, S., Chandrasekaran, A. R., Chakraborty, B., & Bhatia, D. (2021). Aptamer-programmed DNA nanodevices for advanced, targeted cancer theranostics. ACS Applied Bio Materials, 4, 5392–5404.

    CAS  Google Scholar 

  29. Bates, P. J., Laber, D. A., Miller, D. M., Thomas, S. D., & Trent, J. O. (2009). Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Experimental and Molecular Pathology, 86, 151–164.

    CAS  Google Scholar 

  30. Abnous, K., Danesh, N. M., Ramezani, M., Yazdian-Robati, R., Alibolandi, M., & Taghdisi, S. M. (2017). A novel chemotherapy drug-free delivery system composed of three therapeutic aptamers for the treatment of prostate and breast cancers in vitro and in vivo. Nanomedicine: Nanotechnology Biology and Medicine, 13, 1933–1940.

    CAS  Google Scholar 

  31. Santos, T., Pereira, P., Campello, M. P. C., Paulo, A., Queiroz, J. A., Cabrita, E., & Cruz, C. (2019). RNA G-quadruplex as supramolecular carrier for cancer-selective delivery. European Journal of Pharmaceutics and Biopharmaceutics, 142, 473–479.

    CAS  Google Scholar 

  32. Lewis, D., Haines, C., & Ross, D. (2011). Protein tyrosine kinase 7: A novel surface marker for human recent thymic emigrants with potential clinical utility. Journal of Perinatology, 31, S72.

    CAS  Google Scholar 

  33. Wang, Y., Luo, Y., Bing, T., Chen, Z., Lu, M., Zhang, N., Shangguan, D., & Gao, X. (2014). DNA aptamer evolved by cell-SELEX for recognition of prostate cancer. PLoS ONE, 9, e100243.

    Google Scholar 

  34. Bing, T., Wang, J., Shen, L., Liu, X., & Shangguan, D. (2020). Prion protein targeted by a prostate cancer cell binding aptamer, a potential tumor marker? ACS Applied Bio Materials, 3, 2658–2665.

    CAS  Google Scholar 

  35. Lee, J., Oh, J., Lee, E.-S., Kim, Y.-P., & Lee, M. (2019). Conjugation of prostate cancer-specific aptamers to polyethylene glycol-grafted polyethylenimine for enhanced gene delivery to prostate cancer cells. Journal of Industrial and Engineering Chemistry, 73, 182–191.

    CAS  Google Scholar 

  36. Kaighn, M., Narayan, K. S., Ohnuki, Y., Lechner, J. F., & Jones, L. (1979). Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Investigative Urology, 17, 16–23.

    CAS  Google Scholar 

  37. Mickey, D. D., Stone, K. R., Wunderli, H., Mickey, G. H., Vollmer, R. T., & Paulson, D. F. (1977). Heterotransplantation of a human prostatic adenocarcinoma cell line in nude mice. Cancer Research, 37, 4049–4058.

    CAS  Google Scholar 

  38. Lima, A. R., Araújo, A. M., Pinto, J., Jerónimo, C., Henrique, R., Bastos, M. D. L., Carvalho, M., & Guedes de Pinho, P. (2018). Discrimination between the human prostate normal and cancer cell exometabolome by GC-MS. Scientific Reports, 8, 1–12.

    Google Scholar 

  39. Ayatollahi, S., Salmasi, Z., Hashemi, M., Askarian, S., Oskuee, R. K., Abnous, K., & Ramezani, M. (2017). Aptamer-targeted delivery of Bcl-xL shRNA using alkyl modified PAMAM dendrimers into lung cancer cells. International Journal of Biochemistry & Cell Biology, 92, 210–217.

    CAS  Google Scholar 

  40. Stoltenburg, R., Reinemann, C., & Strehlitz, B. (2005). FluMag-SELEX as an advantageous method for DNA aptamer selection. Analytical and Bioanalytical Chemistry, 383, 83–91.

    CAS  Google Scholar 

  41. Askarian, S., Abnous, K., Taghavi, S., Oskuee, R. K., & Ramezani, M. (2015). Cellular delivery of shRNA using aptamer-conjugated PLL-alkyl-PEI nanoparticles. Colloids and Surfaces. B Biointerfaces, 136, 355–364.

    CAS  Google Scholar 

  42. Salatin, S., Maleki Dizaj, S., & Yari Khosroushahi, A. (2015). Effect of the surface modification, size, and shape on cellular uptake of nanoparticles. Cell Biology International, 39, 881–890.

    CAS  Google Scholar 

  43. González-Domínguez, I., Grimaldi, N., Cervera, L., Ventosa, N., & Gòdia, F. (2019). Impact of physicochemical properties of DNA/PEI complexes on transient transfection of mammalian cells. New Biotechnology, 49, 88–97.

    Google Scholar 

  44. Kim, J. A., Åberg, C., Salvati, A., & Dawson, K. A. (2012). Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population. Nature Nanotechnology, 7, 62.

    CAS  Google Scholar 

  45. Oskuee, R. K., Dabbaghi, M., Gholami, L., Taheri-Bojd, S., Balali-Mood, M., Mousavi, S. H., & Malaekeh-Nikouei, B. (2018). Investigating the influence of polyplex size on toxicity properties of polyethylenimine mediated gene delivery. Life Sciences, 197, 101–108.

    Google Scholar 

  46. Powell, D., Chandra, S., Dodson, K., Shaheen, F., Wiltz, K., Ireland, S., Syed, M., Dash, S., Wiese, T., Mandal, T., et al. (2017). Aptamer-functionalized hybrid nanoparticle for the treatment of breast cancer. European Journal of Pharmaceutics and Biopharmaceutics, 114, 108–118.

    CAS  Google Scholar 

  47. Taghavi, S., Ramezani, M., Alibolandi, M., Abnous, K., & Taghdisi, S. M. (2017). Chitosan-modified PLGA nanoparticles tagged with 5TR1 aptamer for in vivo tumor-targeted drug delivery. Cancer Letters, 400, 1–8.

    CAS  Google Scholar 

  48. Wilkosz, N., Jamróz, D., Kopec, W., Nakai, K., Yusa, S.-I., Wytrwal-Sarna, M., Bednar, J., Nowakowska, M., & Kepczynski, M. (2017). Effect of polycation structure on interaction with lipid membranes. The Journal of Physical Chemistry B, 121, 7318–7326.

    CAS  Google Scholar 

  49. Kennedy, D. C., Gies, V., Jezierski, A., & Yang, L. (2019). Changes in the physical properties of silver nanoparticles in cell culture media mediate cellular toxicity and uptake. Journal of Nanoparticle Research, 21, 132.

    Google Scholar 

  50. Firlej, V., Soyeux, P., Nourieh, M., Huet, E., Semprez, F., Allory, Y., Londono-Vallejo, A., de la Taille, A., Vacherot, F., & Destouches, D. (2022). Overexpression of nucleolin and associated genes in prostate cancer. International Journal of Molecular Sciences, 23, 4491.

    CAS  Google Scholar 

  51. Zhang, H., Wang, A., Qi, S., Cheng, S., Yao, B., & Xu, Y. (2014). Protein tyrosine kinase 7 (PTK7) as a predictor of lymph node metastases and a novel prognostic biomarker in patients with prostate cancer. International Journal of Molecular Sciences, 15, 11665–11677.

    CAS  Google Scholar 

  52. Noaparast, Z., Hosseinimehr, S. J., Piramoon, M., & Abedi, S. M. (2015). Tumor targeting with a 99mTc-labeled AS1411 aptamer in prostate tumor cells. Journal of Drug Targeting, 23, 497–505.

    CAS  Google Scholar 

  53. Huang, Y., Liu, X., Zhang, L., Hu, K., Zhao, S., Fang, B., Chen, Z.-F., & Liang, H. (2015). Nicking enzyme and graphene oxide-based dual signal amplification for ultrasensitive aptamer-based fluorescence polarization assays. Biosensors & Bioelectronics, 63, 178–184.

    CAS  Google Scholar 

  54. Chen, F., Liu, Y., Liao, R., Gong, H., Chen, C., Chen, X., & Cai, C. (2017). Reduced graphene oxide as a resonance light-scattering probe for thrombin detection using dual-aptamer-based dsDNA. Analytica Chimica Acta, 985, 141–147.

    CAS  Google Scholar 

  55. Kafil, V., & Omidi, Y. (2011). Cytotoxic impacts of linear and branched polyethylenimine nanostructures in A431 cells. BioImpacts: BI, 1, 23.

    CAS  Google Scholar 

  56. Kaur, H., Bruno, J. G., Kumar, A., & Sharma, T. K. (2018). Aptamers in the therapeutics and diagnostics pipelines. Theranostics, 8, 4016.

    CAS  Google Scholar 

  57. Shahidi-Hamedani, N., Shier, W. T., Moghadam Ariaee, F., Abnous, K., & Ramezani, M. (2013). Targeted gene delivery with noncovalent electrostatic conjugates of sgc-8c aptamer and polyethylenimine. The Journal of Gene Medicine, 15, 261–269.

    CAS  Google Scholar 

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Acknowledgements

This study was funded by Mashhad University of Medical Sciences, Mashhad, Iran (No. 961395).

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Correspondence to Reza Kazemi Oskuee.

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Askarian, S., Nasab, N.K., Aghaee-Bakhtiari, S.H. et al. Investigating Efficacy of Three DNA-Aptamers in Targeted Plasmid Delivery to Human Prostate Cancer Cell Lines. Mol Biotechnol 65, 97–107 (2023). https://doi.org/10.1007/s12033-022-00528-7

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