Skip to main content
Log in

Crocin-loaded zein beta-cyclodextrin nanoparticles: a promising strategy for inducing apoptosis in pancreatic cancer cells

  • Original Article
  • Published:
Emergent Materials Aims and scope Submit manuscript

Abstract

Nanotechnology is a promising field for developing drug delivery systems that can enhance therapeutic efficacy. In this study, we aimed to create crocin-loaded zein beta-cyclodextrin nanoparticles (CrZeCD-NPs) to evaluate the expression of genes associated with apoptosis. The nanoparticles were synthesized by encapsulating crocin within zein beta-cyclodextrin, a biocompatible and biodegradable polymer. We extensively characterized the physicochemical properties of the nanoparticles using techniques such as dynamic light scattering (DLS), zeta potential (ZP), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) to evaluate their size distribution, morphology, and drug loading efficiency. Finally, we examined the cytotoxicity potential and ability of the formulation to induce apoptosis using fluorescent microscopy, flow cytometry, and real-time qPCR. The characterized nanoparticles had an average diameter of 165 nm with a narrow size distribution (zeta potential, − 8.05 mV; PDI, 0.24), indicating their potential as a drug delivery system. The encapsulation efficiency of crocin was found to be 96%, indicating successful loading of the drug within the nanoparticles. The anticancer properties of CrZeCD-NPs were tested, and they were found to significantly inhibit pancreatic cancer (IC50 = 22.6 µg/ml) without showing any toxic impact on Huvec as a normal cell. The highest level of apoptosis was shown at the concentration of 66 µg/mL in flow cytometry and fluorescent investigation. The real-time analysis demonstrated a significant upregulation of pro-apoptotic genes, including caspase 9 and p53, indicating the potential of crocin-loaded zein beta-cyclodextrin nanoparticles in promoting apoptosis. Based on this experiment, it can be concluded that CrZeCD-NPs may be suitable for future anti-cancer treatments. However, additional studies are necessary to investigate the efficacy and therapeutic potential of these nanoparticles in vivo. These studies could pave the way for future advancements in cancer treatment.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

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

Similar content being viewed by others

Data availability

The datasets generated during and analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. J.D. Mizrahi et al., Pancreatic cancer 395 (10242), 2008–2020 (2020)

  2. T. Conroy, J.B. Bachet, A. Ayav, F. Huguet, A. Lambert, C. Caramella, R. Maréchal, J.L. Van Laethem, M. Ducreux, Current standards and new innovative approaches for treatment of pancreatic cancer. Eur J Cancer 57, 10–22 (2016). https://doi.org/10.1016/j.ejca.2015.12.026

    Article  PubMed  Google Scholar 

  3. M. Ducreux et al., Systemic treatment of pancreatic cancer revisited in Seminars in Oncology. Elsevier (2019)

  4. I. Garrido-Laguna, M.J.N.r.C.o Hidalgo, Pancreatic cancer: from state-of-the-art treatments to promising novel therapies 12(6), 319–334 (2015)

  5. P. Garcia-Oliveira et al., Status and challenges of plant-anticancer compounds in cancer treatment 14(2), 157 (2021)

  6. F. Majoloet al., Medicinal plants and bioactive natural compounds for cancer treatment: important advances for drug discovery 31, 196–207 (2019)

  7. M. Rameshrad, B. M. Razavi, H. Hosseinzadeh, Saffron and its derivatives, crocin, crocetin and safranal: A patent review 28(2), 147–165 (2018)

  8. B. M. Razavi, H. Hosseinzadeh, Agriculture, Saffron: a promising natural medicine in the treatment of metabolic syndrome 97(6), 1679–1685 (2017)

  9. M. Bhia et al., Saffron (crocins) against cancer, p. 323–365 (2021)

  10. S. Tavasoli et al., Crocin-loaded nanocarriers; approaches and applications, p. 101099 (2023)

  11. E. Mirhadi, H. Nassirli, B. Malaekeh-Nikouei, An updated review on therapeutic effects of nanoparticle-based formulations of saffron components (safranal, crocin, and crocetin) 50, 47–58 (2020)

  12. M. Saeedi et al., Applications of nanotechnology in drug delivery to the central nervous system 111, 666–675 (2019)

  13. R. Penalva et al., Zein nanoparticles for oral delivery of quercetin: Pharmacokinetic studies and preventive anti-inflammatory effects in a mouse model of endotoxemia 13(1), 103–110 (2017)

  14. G. Labib, Overview on zein protein: A promising pharmaceutical excipient in drug delivery systems and tissue engineering 15(1), 65–75 (2018)

  15. T. Karpkird et al., A novel chitosan-citric acid crosslinked beta-cyclodextrin nanocarriers for insoluble drug delivery 498p. 108184 (2020)

  16. Y. Kiraz et al., Major apoptotic mechanisms and genes involved in apoptosis 378471–8486 (2016)

  17. H. Mollaei et al., The anti-proliferative and apoptotic effects of crocin on chemosensitive and chemoresistant cervical cancer cells 94, 307–316 (2017)

  18. N.M. Elsherbiny et al., Chemo-preventive effect of crocin against experimentally-induced hepatocarcinogenesis via regulation of apoptotic and Nrf2 signaling pathways 80103494 (2020)

  19. A. Nasimian et al., Cytosolic and mitochondrial ROS production resulted in apoptosis induction in breast cancer cells treated with crocin: the role of FOXO3a, PTEN and AKT signaling 177, 113999 (2020)

  20. Q. Zhong, M. Jin, Zein nanoparticles produced by liquid–liquid dispersion 23(8), 2380–2387 (2009)

  21. A.K. Tyagi et al., Identification of a novel compound (β-sesquiphellandrene) from turmeric (Curcuma longa) with anticancer potential: comparison with curcumin 331175–1186 (2015)

  22. M.H. Tabrizi, M. Soltani, A.J.J.o.M.L, Es-haghi, Preparation and characterization of the farnesiferol C-loaded solid lipid nanoparticles decorated with folic acid-bound chitosan and evaluation of its in vitro anti-cancer and anti-angiogenic activities 382,121908 (2023)

  23. S. Bhattacharjee, DLS and zeta potential–what they are and what they are not? 235, 337–351 (2016)

  24. S. Samarghandian, A. Borji, Anticarcinogenic effect of saffron (Crocus sativus L.) and its ingredients 6(2), 99 (2014)

  25. S. Rahaiee et al., Nanoparticles based on crocin loaded chitosan-alginate biopolymers: antioxidant activities, bioavailability and anticancer properties 99, 401–408 (2017)

  26. P. Majtnerová, T. Roušar, An overview of apoptosis assays detecting DNA fragmentation 45(5), 1469–1478 (2018)

  27. N. Atale et al., Cell‐death assessment by fluorescent and nonfluorescent cytosolic and nuclear staining techniques 255(1), 7–19 (2014)

  28. H. Chavoshi et al., Crocin-loaded liposomes sensitize MDA-MB 231 breast cancer cells to doxorubicin by inducing apoptosis 130272–280 (2023)

  29. L. Lossi, C. Castagna, A. Merighi, Caspase-3 mediated cell death in the normal development of the mammalian cerebellum 19(12), 3999 (2018)

  30. B.J. Aubrey et al., How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? 25(1), 104–113 (2018)

  31. L. Deng et al., Crocin inhibits proliferation and induces apoptosis through suppressing MYCN expression in retinoblastoma 33(5), e22292 (2019)

  32. Y. Liu et al., Crocin improves endometriosis by inhibiting cell proliferation and the release of inflammatory factors 106, 1678–1685 (2018)

  33. D. Esposito et al., Mucoadhesive zein/beta-cyclodextrin nanoparticles for the buccal delivery of curcumin 586, 119587 (2020)

  34. A. Jain et al., Beta carotene-loaded zein nanoparticles to improve the biopharmaceutical attributes and to abolish the toxicity of methotrexate: a preclinical study for breast cancer 46(sup1), 402–412 (2018)

Download references

Acknowledgements

The authors are grateful to the Islamic Azad University of Mashhad for the laboratory facilities.

Author information

Authors and Affiliations

Authors

Contributions

AV: study design, experimental work, formal analysis, and writing original draft; EK and HB: analysis, methodology, project administration, supervision, review, and editing of the original draft; all authors read and approved the final manuscript. All authors contributed equally to this work.

Corresponding author

Correspondence to Ehsan Karimi.

Ethics declarations

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Not applicable.

Competing interests

The authors declare no competing interests.

Research involving human participants and/or animals

Not applicable.

Additional information

Arezoo Vedad, Ehsan Karimi and Hilda Besharat contributed equally to this work.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) 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

Vedad, A., Karimi, E. & Besharat, H. Crocin-loaded zein beta-cyclodextrin nanoparticles: a promising strategy for inducing apoptosis in pancreatic cancer cells. emergent mater. (2024). https://doi.org/10.1007/s42247-024-00700-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s42247-024-00700-6

Keywords

Navigation