Log in

Folic Acid-Conjugated Iron Oxide Magnetic Nanoparticles Based on Bovine Serum Albumin (BSA) for Targeted Delivery of Curcumin to Suppress Liver Cancer Cells

  • Original Article
  • Published:
Chemistry Africa Aims and scope Submit manuscript

Abstract

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this study, magnetic iron oxide nanoparticles coated with bovine serum albumin (BSA) and targeted by folic acid were synthesized and evaluated as carriers to deliver curcumin to the cells and its anti-cancer effects on liver cancer cells (HepG2) were investigated in vitro.

Methods

Stabilized iron oxide magnetic nanoparticles were synthesized in a single container. The folic acid targeting agent was then ligated to BSA protein, using carbide amide chemistry. After loading of curcumin, the construct and its characteristics were studied through VSM, DLS, FTIR, TEM, UV–Vis and hemolysis techniques. By combining fluorophore dyes to the final system, the amount of cellular uptake and active drug delivery was measured. Finally, the anti-cancer effects of this nanostructure were evaluated by MTT and apoptosis assays.

Results

Iron oxide nanoparticles with dimensions between 95 and 185 nm were prepared. The morphology of the final nanostructure showed to be predominantly spherical. The results of characterization of nanoparticles showed that BSA-coated magnetic iron oxide nanoparticles, targeted with folic acid, were properly synthesized and curcumin was loaded into the nanostructure. The results of nanostructure cell uptake using flow cytometry showed that nanoparticles enter the cell highly efficient. MTT and cell apoptosis showed that treatment with this nanostructure reduced the cell survival and induced apoptosis in HepG2 cancer cells.

Conclusion

Folic acid-conjugated iron oxide magnetic nanoparticles stabilized by BSA were successfully synthesized and showed a good loading and release efficacy for delivery of curcumin to the target liver cancer cells. Folic acid conjugation increased the liver cancer cell characteristics inhibition. The nanoparticles indicated to have good cell entry properties and showed to significantly suppress HepG2 cancer cells in vitro. These nanostructures could be used for synergized co-therapy with irradiation due to the magnetic properties of particles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Spain)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability Statement

The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Oun R, Moussa YE, Wheate NJ (2018) The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans 47(19):6645–6653

    Article  CAS  PubMed  Google Scholar 

  2. Chen J, Ning C, Zhou Z, Yu P, Zhu Y, Tan G et al (2019) Nanomaterials as photothermal therapeutic agents. Prog Mater Sci 99:1–26

    Article  PubMed  Google Scholar 

  3. Olusanya TO, Haj Ahmad RR, Ibegbu DM, Smith JR, Elkordy AA (2018) Liposomal drug delivery systems and anticancer drugs. Molecules 23(4):907

    Article  PubMed Central  Google Scholar 

  4. Rabinow BE (2004) Nanosuspensions in drug delivery. Nat Rev Drug Discov 3(9):785–796

    Article  CAS  PubMed  Google Scholar 

  5. Mokwena MG, Kruger CA, Ivan M-T, Heidi A (2018) A review of nanoparticle photosensitizer drug delivery uptake systems for photodynamic treatment of lung cancer. Photodiagn Photodyn Ther 22:147–154

    Article  CAS  Google Scholar 

  6. Shah A, Aftab S, Nisar J, Ashiq MN, Iftikhar FJ (2021) Nanocarriers for targeted drug delivery. J Drug Deliv Sci Technol 62:102426

    Article  CAS  Google Scholar 

  7. Gharbavi M, Johari B, Eslami SS, Mousazadeh N, Sharafi A (2020) Cholesterol-conjugated bovine serum albumin nanoparticles as a tamoxifen tumor-targeted delivery system. Cell Biol Int 44(12):2485–2498

    Article  CAS  PubMed  Google Scholar 

  8. Goel S, Ni D, Cai W (2017) Harnessing the power of nanotechnology for enhanced radiation therapy. ACS Nano 11(6):5233–5237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rabin O, Manuel Perez J, Grimm J, Wojtkiewicz G, Weissleder R (2006) An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater 5(2):118–122

    Article  CAS  PubMed  Google Scholar 

  10. Yao M-H, Ma M, Chen Y, Jia X-Q, Xu G, Xu H-X et al (2014) Multifunctional Bi2S3/PLGA nanocapsule for combined HIFU/radiation therapy. Biomaterials 35(28):8197–8205

    Article  CAS  PubMed  Google Scholar 

  11. Gharbavi M, Johari B, Mousazadeh N, Rahimi B, Leilan MP, Eslami SS et al (2020) Hybrid of niosomes and bio-synthesized selenium nanoparticles as a novel approach in drug delivery for cancer treatment. Mol Biol Rep 47(9):6517–6529

    Article  CAS  PubMed  Google Scholar 

  12. Pamies R, Cifre JGH, Espín VF, Collado-González M, Baños FGD, de la Torre JG (2014) Aggregation behaviour of gold nanoparticles in saline aqueous media. J Nanopart Res 16(4):1–11

    Article  Google Scholar 

  13. Gharbavi M, Johari B, Rismani E, Mousazadeh N, Taromchi AH, Sharafi A (2020) NANOG decoy oligodeoxynucleotide–encapsulated niosomes nanocarriers: a promising approach to suppress the metastatic properties of U87 human glioblastoma multiforme cells. ACS Chem Neurosci 11(24):4499–4515

    Article  CAS  PubMed  Google Scholar 

  14. Nabati F, Moradi M, Mohabatkar H (2020) In silico analyzing the molecular interactions of plant-derived inhibitors against E6AP, p53, and c-Myc binding sites of HPV type 16 E6 oncoprotein. Mol Biol Res Commun 9(2):71

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB (2008) Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett 267(1):133–164

    Article  CAS  PubMed  Google Scholar 

  16. Amekyeh H, Alkhader E, Sabra R, Billa N (2022) Prospects of curcumin nanoformulations in cancer management. Molecules 27(2):361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ding C, Xu Y, Zhao Y, Zhong H, Luo X (2018) Fabrication of BSA@ AuNC-based nanostructures for cell fluoresce imaging and target drug delivery. ACS Appl Mater Interfaces 10(10):8947–8954

    Article  CAS  PubMed  Google Scholar 

  18. Nosrati H, Davaran S, Kheiri Manjili H, Rezaeejam H, Danafar H (2019) Bovine serum albumin stabilized iron oxide and gold bimetallic heterodimers: synthesis, characterization and Stereological study. Appl Organomet Chem 33(10):e5155

    Article  Google Scholar 

  19. Smith BJ, Popplewell A, Athwal D, Chapman AP, Heywood S, West SM et al (2001) Prolonged in vivo residence times of antibody fragments associated with albumin. Bioconjug Chem 12(5):750–756

    Article  CAS  PubMed  Google Scholar 

  20. Wen AM, Lee KL, Cao P, Pangilinan K, Carpenter BL, Lam P et al (2016) Utilizing viral nanoparticle/dendron hybrid conjugates in photodynamic therapy for dual delivery to macrophages and cancer cells. Bioconjug Chem 27(5):1227–1235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pang J, Li Z, Li S, Lin S, Wang H, **e Q et al (2018) Folate-conjugated zein/Fe3O4 nanocomplexes for the enhancement of cellular uptake and cytotoxicity of gefitinib. J Mater Sci 53(21):14907–14921

    Article  CAS  Google Scholar 

  22. Ghaznavi H, Hosseini-Nami S, Kamrava SK, Irajirad R, Maleki S, Shakeri-Zadeh A et al (2018) Folic acid conjugated PEG coated gold–iron oxide core–shell nanocomplex as a potential agent for targeted photothermal therapy of cancer. Artif Cells Nanomed Biotechnol 46(8):1594–1604

    CAS  PubMed  Google Scholar 

  23. Fan W, Xu Y, Li Z, Li Q (2019) Folic acid-modified β-cyclodextrin nanoparticles as drug delivery to load DOX for liver cancer therapeutics. Soft Mater 17(4):437–447

    Article  CAS  Google Scholar 

  24. Nosrati H, Sefidi N, Sharafi A, Danafar H, Manjili HK (2018) Bovine serum albumin (BSA) coated iron oxide magnetic nanoparticles as biocompatible carriers for curcumin-anticancer drug. Bioorg Chem 76:501–509

    Article  CAS  PubMed  Google Scholar 

  25. Gharbavi M, Sharafi A, Motamed Fath P, Oruji S, Pakzad H, Kheiri Manjili H (2021) Formulation and biocompatibility of microemulsion-based PMBN as an efficient system for paclitaxel delivery. J Appl Biotechnol Rep 8(1). https://doi.org/10.30491/jabr.2020.114985

    Article  Google Scholar 

  26. Faghfoori MH, Nosrati H, Rezaeejam H, Charmi J, Kaboli S, Johari B et al (2020) Anticancer effect of X-ray triggered methotrexate conjugated albumin coated bismuth sulfide nanoparticles on SW480 colon cancer cell line. Int J Pharm 582:119320

    Article  CAS  PubMed  Google Scholar 

  27. Mousazadeh N, Gharbavi M, Rashidzadeh H, Nosrati H, Danafar H, Johari B (2022) Anticancer evaluation of methotrexate and curcumin-coencapsulated niosomes against colorectal cancer cell lines. Nanomedicine 17(4):201–217

    Article  CAS  PubMed  Google Scholar 

  28. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR (2019) A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 16(10):589–604

    Article  PubMed  PubMed Central  Google Scholar 

  29. Gerbes A, Zoulim F, Tilg H, Dufour J-F, Bruix J, Paradis V et al (2018) Gut roundtable meeting paper: selected recent advances in hepatocellular carcinoma. Gut 67(2):380–388

    Article  CAS  PubMed  Google Scholar 

  30. Walters CL, Arend RC, Armstrong DK, Naumann RW, Alvarez RD (2013) Folate and folate receptor alpha antagonists mechanism of action in ovarian cancer. Gynecol Oncol 131(2):493–498

    Article  CAS  PubMed  Google Scholar 

  31. Zhang J, Zhao X, **an M, Dong C, Shuang S (2018) Folic acid-conjugated green luminescent carbon dots as a nanoprobe for identifying folate receptor-positive cancer cells. Talanta 183:39–47

    Article  CAS  PubMed  Google Scholar 

  32. Gao B, Shen L, He K-W, **ao W-H (2015) GNRs@ SiO2-FA in combination with radiotherapy induces the apoptosis of HepG2 cells by modulating the expression of apoptosis-related proteins. Int J Mol Med 36(5):1282–1290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jurczyk M, Jelonek K, Musiał-Kulik M, Beberok A, Wrześniok D, Kasperczyk J (2021) Single-versus dual-targeted nanoparticles with folic acid and biotin for anticancer drug delivery. Pharmaceutics 13(3):326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153(3):198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yang R, An Y, Miao F, Li M, Liu P, Tang Q (2014) Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo. Int J Nanomed 9:4231

    Article  Google Scholar 

  36. Hao H, Ma Q, He F, Yao P (2014) Doxorubicin and Fe3O4 loaded albumin nanoparticles with folic acid modified dextran surface for tumor diagnosis and therapy. J Mater Chem B 2(45):7978–7987

    Article  CAS  PubMed  Google Scholar 

  37. AbouAitah K, Swiderska-Sroda A, Farghali AA, Wojnarowicz J, Stefanek A, Gierlotka S et al (2018) Folic acid–conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action. Oncotarget 9(41):26466

    Article  PubMed  PubMed Central  Google Scholar 

  38. Nosrati H, Salehiabar M, Manjili HK, Danafar H, Davaran S (2018) Preparation of magnetic albumin nanoparticles via a simple and one-pot desolvation and co-precipitation method for medical and pharmaceutical applications. Int J Biol Macromol 108:909–915

    Article  CAS  PubMed  Google Scholar 

  39. Zhou Y, Hua S, Yu J, Dong P, Liu F, Hua D (2015) A strategy for effective radioprotection by chitosan-based long-circulating nanocarriers. J Mater Chem B 3(15):2931–2934

    Article  CAS  PubMed  Google Scholar 

  40. Nabati Souha L, Alebrahim MT, Habibi Yangjeh A, Feizpoor S (2021) Green synthesis of iron oxide nanoparticles (Fe3O4) by extract of aerial organs of Russian knapweed (Acroptilon repens L.). Cell Mol Res (Iran J Biol) (in press)

  41. Nosrati H, Baghdadchi Y, Abbasi R, Barsbay M, Ghaffarlou M, Abhari F et al (2021) Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model. J Mater Chem B 9(22):4510–4522

    Article  CAS  PubMed  Google Scholar 

  42. Zhang H, Li J, Hu Y, Shen M, Shi X, Zhang G (2016) Folic acid-targeted iron oxide nanoparticles as contrast agents for magnetic resonance imaging of human ovarian cancer. j Ovar Res 9(1):1–8

    Google Scholar 

  43. Nosrati H, Charmi J, Abhari F, Attari E, Bochani S, Johari B et al (2020) Improved synergic therapeutic effects of chemoradiation therapy with the aid of a co-drug-loaded nano-radiosensitizer under conventional-dose X-ray irradiation. Biomater Sci 8(15):4275–4286

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by the Zanjan University of Medical Sciences (Grant number: A-12-1244-7, Ethical code: IR.ZUMS.REC.1398.0140).

Author information

Authors and Affiliations

Authors

Contributions

HF: investigation, methodology. BJ: conceptualization, formal analysis, investigation, methodology, visualization, writing—original draft, writing—review and editing. MM: writing—original draft, review and editing. MG: formal analysis, investigation, methodology. HD: visualization, investigation, methodology.

Corresponding author

Correspondence to Behrooz Johari.

Ethics declarations

Conflict of interest

The authors declare there is no potential conflict of interests that could negatively influence this study.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Felenji, H., Johari, B., Moradi, M. et al. Folic Acid-Conjugated Iron Oxide Magnetic Nanoparticles Based on Bovine Serum Albumin (BSA) for Targeted Delivery of Curcumin to Suppress Liver Cancer Cells. Chemistry Africa 5, 1627–1639 (2022). https://doi.org/10.1007/s42250-022-00425-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42250-022-00425-1

Keywords

Navigation