Iranian Journal of Medical Sciences

Document Type : Original Article(s)

Authors

1 Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran

2 Department of Medical Biotechnology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran

3 Department of Medical Biotechnology, Zanjan University of Medical Sciences, Zanjan, Iran

4 Department of Medical Genetics and Biotechnology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran

10.30476/ijms.2026.108826.4394

Abstract

Background: Selenium nanoparticles (SeNPs), compared to other forms of selenium, have shown promising antioxidant and anticancer properties with lower toxicity. However, SeNPs precipitate and aggregate in aqueous solutions due to their high surface energy. To overcome this limitation and improve stability, solubility, and enhance biological efficacy, we functionalized them with L-asparagine/tartaric acid (Asn-Tar). This study aimed to evaluate the antimicrobial, cytotoxic, and antioxidant properties of SeNPs conjugated to Asn-Tar on MDA-MB-231 breast cancer cells.
Methods: This study was conducted at Lorestan, Iran, in 2023. SeNPs were synthesized using a co-precipitation method and then coated with Asn-Tar. Structural characterization was performed using Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Dynamic light scattering (DLS), zeta potential analysis, and Ultraviolet-visible (UV-Vis) spectroscopy. Antioxidant activity was assessed. For biological evaluation, an in vitro experimental design was employed. Cytotoxicity against MDA-MB-231 breast cancer cells and normal fibroblast cells at various pH levels was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with three independent replicates per concentration (n=3). Antimicrobial activity against a panel of Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains, was evaluated in triplicate using broth microdilution and well diffusion methods. Quantitative data are presented as mean±SD. Statistical significance was determined using Student’s t test and one-way ANOVA, with P<0.05 considered significant.
Results: The synthesized Asn-Tar/SeNPs nanocomposite exhibited a spherical morphology with an average size of 460.8 nm, a negative zeta potential (-9.37±0.44 mV), and successful coating was confirmed by FTIR and XRD. The nanocomposite demonstrated dose-dependent antioxidant activity, with an IC₅₀ of 22.73±1.55 µg/mL in the DPPH assay. It exhibited potent and selective cytotoxicity against MDA-MB-231 breast cancer cells (IC₅₀=3.47±0.28 µg/mL) compared to normal fibroblast cells (IC₅₀=5.91±0.34 µg/mL; P=0.0051). The nanocomposite retained approximately 50% of its cytotoxic activity at acidic pH (4.5). Furthermore, it showed strong antimicrobial activity, with inhibition zones up to 36.9±1.2 mm against Staphylococcus saprophyticus and MIC values as low as 0.035 mg/mL against Pseudomonas aeruginosa.
Conclusion: The produced Asn-Tar/SeNPs nanocomposite exhibited potent antimicrobial, selective cytotoxicity, and antioxidant properties. Our findings confirm the potential of these Asn-Tar/SeNPs nanocomposites for targeted therapy of breast cancer.

Highlights

Abdolrazagh Marzban (Google Scholar)
Hamed Esmaeil Lashgarian (Google Scholar)  

Keywords

  1. Chehelgerdi M, Chehelgerdi M, Allela OQB, Pecho RDC, Jayasankar N, Rao DP, et al. Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol Cancer. 2023;22:169. doi: 10.1186/s12943-023-01865-0. PubMed PMID: 37814270; PubMed Central PMCID: PMC10561438.
  2. Sengar A. The Role of Nanotechnology in Revolutionizing Cancer Treatment. Preprints. 2025. doi: 10.20944/preprints202503.0713.v1.
  3. Eltaib L. Polymeric Nanoparticles in Targeted Drug Delivery: Unveiling the Impact of Polymer Characterization and Fabrica-tion. Polymers (Basel). 2025;17. doi: 10.3390/polym17070833. PubMed PMID: 40219222; PubMed Central PMCID: PMC11991310.
  4. Anjum S, Hashim M, Imran M, Babur S, Adnan S, Hano C, et al. Selenium Nanoparticles in Cancer Therapy: Unveiling Cytotoxic Mechanisms and Therapeutic Potential. Cancer Rep (Hoboken). 2025;8:e70210. doi: 10.1002/cnr2.70210. PubMed PMID: 40452566; PubMed Central PMCID: PMC12127775.
  5. Waqar MA. A comprehensive review on recent advancements in drug delivery via selenium nanoparticles. J Drug Target. 2025;33:157-70. doi: 10.1080/1061186X.2024.2412142. PubMed PMID: 39392210.
  6. Chen W, Cheng H, Xia W. Progress in the Surface Functionalization of Selenium Nanoparticles and Their Potential Applica-tion in Cancer Therapy. Antioxidants (Basel). 2022;11. doi: 10.3390/antiox11101965. PubMed PMID: 36290687; PubMed Central PMCID: PMC9598587.
  7. Bisht N, Phalswal P, Khanna PK. Selenium nanoparticles: a review on synthesis and biomedical applications. Mater Adv. 2022;3:1415-31. doi: 10.1039/D1MA00639H.
  8. Handy DE, Joseph J, Loscalzo J. Selenium, a Micronutrient That Modulates Cardiovascular Health via Redox Enzymology. Nutrients. 2021;13. doi: 10.3390/nu13093238. PubMed PMID: 34579115; PubMed Central PMCID: PMC8471878.
  9. Candido AC, Azevedo FM, Machamba AAL, Pinto CA, Lopes SO, de Souza Macedo M, et al. Implications of iodine deficiency by gestational trimester: a systematic review. Arch Endocrinol Metab. 2021;64:507-13. doi: 10.20945/2359-3997000000289. PubMed PMID: 34033289; PubMed Central PMCID: PMC10118970.
  10. Raja P, Rajkumar P, Jegatheesan P, Amalraj AS, Rajah AJL. Investigation of structural, optical and photoluminescence properties of non-essential amino acid capped zinc sulfide nanoparticles for optoelectronic applications. J Indian Chem Soc. 2023;100:100855. doi: 10.1016/j.jics.2022.100855.
  11. Li M, Su J, Yang H, Feng L, Wang M, Xu G, et al. Grape tartaric acid: chemistry, function, metabolism, and regulation. Horticulturae. 2023;9:1173. doi: 10.3390/horticulturae9111173.
  12. Jantwal A, Durgapal S, Upadhyay J, Joshi T, Kumar A. Tartaric acid. In: Antioxidants effects in health. Amsterdam: Elsevier; 2022. p. 485-92. doi: 10.1016/B978-0-12-819096-8.00013-6.
  13. Weinstein MP, Lewis JS, 2nd. The Clinical and Laboratory Standards Institute Subcommittee on Antimicrobial Susceptibility Testing: Background, Organization, Functions, and Processes. J Clin Microbiol. 2020;58. doi: 10.1128/JCM.01864-19. PubMed PMID: 31915289; PubMed Central PMCID: PMC7041576.
  14. Bartosiak M, Giersz J, Jankowski K. Analytical monitoring of selenium nanoparticles green synthesis using photochemical vapor generation coupled with MIP-OES and UV-Vis spectrophotometry. Microchem J. 2019;145:1169-75. doi: 10.1016/j.microc.2018.12.024.
  15. Prasad KS, Patel H, Patel T, Patel K, Selvaraj K. Biosynthesis of Se nanoparticles and its effect on UV-induced DNA damage. Colloids Surf B Biointerfaces. 2013;103:261-6. doi: 10.1016/j.colsurfb.2012.10.029. PubMed PMID: 23201746.
  16. Ramamurthy C, Sampath KS, Arunkumar P, Kumar MS, Sujatha V, Premkumar K, et al. Green synthesis and characterization of selenium nanoparticles and its augmented cytotoxicity with doxorubicin on cancer cells. Bioprocess Biosyst Eng. 2013;36:1131-9. doi: 10.1007/s00449-012-0867-1. PubMed PMID: 23446776.
  17. Dhanraj G, Rajeshkumar S. Anticariogenic effect of selenium nanoparticles synthesized using Brassica oleracea. J Nanomater. 2021;2021:8115585. doi: 10.1155/2021/8115585.
  18. Alallam B, Oo MK, Nasir MHM, Taher M. Influence of nanoparticles surface coating on physico-chemical properties for CRISPR gene delivery. J Drug Deliv Sci Technol. 2021;66:102910. doi: 10.1016/j.jddst.2021.102910.
  19. Gauggel S, Derreza-Greeven C, Wimmer J, Wingfield M, van der Burg B, Dietrich DR. Characterization of biologically available wood combustion particles in cell culture medium. ALTEX. 2012;29:183-200. doi: 10.14573/altex.2012.2.183. PubMed PMID: 22562490.
  20. Hernandez-Diaz JA, Garza-Garcia JJ, Leon-Morales JM, Zamudio-Ojeda A, Arratia-Quijada J, Velazquez-Juarez G, et al. Antibacterial Activity of Biosynthesized Selenium Nanoparticles Using Extracts of Calendula officinalis against Potentially Clinical Bacterial Strains. Molecules. 2021;26. doi: 10.3390/molecules26195929. PubMed PMID: 34641478; PubMed Central PMCID: PMC8513099.
  21. Zhang H, Li Z, Dai C, Wang P, Fan S, Yu B, et al. Antibacterial properties and mechanism of selenium nanoparticles synthe-sized by Providencia sp. DCX. Environ Res. 2021;194:110630. doi: 10.1016/j.envres.2020.110630. PubMed PMID: 33345899.
  22. Bu Q, Jiang D, Yu Y, Deng Y, Chen T, Xu L. Surface chemistry engineered selenium nanoparticles as bactericidal and immuno-modulating dual-functional agents for combating methicillin-resistant Staphylococcus aureus Infection. Drug Resist Updat. 2024;76:101102. doi: 10.1016/j.drup.2024.101102. PubMed PMID: 38936006.
  23. Lakshmi T, Rajeshkumar S, Dinesh G. Green synthesis of selenium nanoparticles using Vaccinium subg. Oxycoccus for antioxidant, anti-inflammatory, and cytotoxic effect. Trop J Pharm Health Res. 2013;13:61-7. doi: 10.21522/TIJPH.2013.13.01.Art061.
  24. Sabzevari AG, Sabahi H, Nikbakht M, Azizi M, Dianat-Moghadam H, Amoozgar Z. Exploring the Potential of Montmorillonite as an Antiproliferative Nanoagent against MDA-MB-231 and MCF-7 Human Breast Cancer Cells. Cells. 2024;13. doi: 10.3390/cells13020200. PubMed PMID: 38275825; PubMed Central PMCID: PMC10814472.
  25. Pi J, Shen L, Yang E, Shen H, Huang D, Wang R, et al. Macrophage-Targeted Isoniazid-Selenium Nanoparticles Promote Antimicrobial Immunity and Synergize Bactericidal Destruction of Tuberculosis Bacilli. Angew Chem Int Ed Engl. 2020;59:3226-34. doi: 10.1002/anie.201912122. PubMed PMID: 31756258.
  26. Hosnedlova B, Kepinska M, Skalickova S, Fernandez C, Ruttkay-Nedecky B, Malevu TD, et al. A Summary of New Findings on the Biological Effects of Selenium in Selected Animal Species-A Critical Review. Int J Mol Sci. 2017;18. doi: 10.3390/ijms18102209. PubMed PMID: 29065468; PubMed Central PMCID: PMC5666889.
  27. İpek P, Baran A, Hatipoğlu A, Baran MF. Cytotoxic potential of selenium nanoparticles (SeNPs) derived from leaf extract of Mentha longifolia L. J Agric Environ Food Sci. 2024;8:169-75. doi: 10.31015/jaefs.2024.1.17.
  28. Gulbay G, Secme M, Ilhan H. Exploring the Potential of Thymoquinone-Stabilized Selenium Nanoparticles: In HEC1B Endometrial Cancer Cells Revealing Enhanced Anticancer Efficacy. ACS Omega. 2023;8:39822-9. doi: 10.1021/acsomega.3c06028. PubMed PMID: 37901525; PubMed Central PMCID: PMC10601430.
  29. Mahmood RI, Al-Taie A, Al-Rahim AM, Mohammed-Salih HS, Ibrahim HA, Albukhaty S, et al. Biogenic synthesized se-lenium nanoparticles combined chitosan nanoparticles controlled lung cancer growth via ROS generation and mito-chondrial damage pathway. Nanotechnol Rev. 2025;14:20250142. doi: 10.1515/ntrev-2025-0142.