Skip to main content

Advertisement

Log in

Evaluation of apoptotic and anti-metastatic effects by modified mesoporous silica nanoparticles (MSNs) with Zn and NH2 containing cisplatin on HT-29 cell line

  • Research paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

Colorectal cancer ranks third in terms of diagnosis and second concerning cancer-related mortality. The current research is aimed to synthesize cisplatin-loaded mesoporous silica nanoparticles modified with NH2 and zinc (Zn-MSN-NH2-CP) through a sol–gel process and test their cytotoxicity against colon cancer cells in vitro. HT-29 and HUVEC cell lines were grown in supplemented DMEM medium. MTT test was used to determine the cytotoxicity of prepared formulations against normal cells as well as cancer cells. Real-time PCR was utilized to assess the expression of the apoptotic genes in HT-29 treated with CP, Zn-MSN-NH2, and Zn-MSN-NH2-CP. Necrosis or early and late apoptosis were also evaluated in cancerous cells through the flow method. Physicochemical characteristics of Zn-MSN-NH2 were assessed by SEM, TEM, DLS, and FT-IR techniques. According to the release profile, surface modification of Zn-MSN-NH2-CP resulted in a more regulated CP release. The Zn-MSN-NH2-CP was more stable at 4 °C. Cancerous cells were significantly affected by the cytotoxic effects of both CP and Zn-MSN-NH2-CP. Zn-MSN-NH2 could also minimize the toxicity of the unbound drug towards normal cells, while considerably increasing its viability. Compared to the controls, the expression of pro-apoptotic genes was enhanced in cells treated with IC50 concentrations of Zn-MSN-NH2-CP and CP, while the expression of BCL-2 mRNA showed a decline. Flow cytometry findings also revealed a substantial increase in the early and late apoptosis in cells treated with Zn-MSN-NH2-CP. These in-vitro findings introduce Zn-MSN-NH2 as a promising nanocarrier for increasing the bioavailability and anti-cancer efficacy of CP in colon cancer cells.

Graphical Abstract

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
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Notes

  1. Colorectal cancer.

  2. Mesoporous silica nanoparticles.

  3. Cisplatin.

  4. 3-Aminopropyl.

  5. Dynamic light scattering.

  6. Transmission electron microscope.

  7. Scanning electron microscope.

  8. Fourier-transform infrared spectroscopy.

  9. Fetal bovine serum.

  10. Analysis of variance.

References

  1. Douaiher J et al (2017) Colorectal cancer—global burden, trends, and geographical variations. J Surg Oncol 115(5):619–630. https://doi.org/10.1002/jso.24578

    Article  Google Scholar 

  2. Siegel RL et al (2020) Colorectal cancer statistics,2020. CA: Cancer J Clin 70(3):145–164. https://doi.org/10.3322/caac.21601

    Article  Google Scholar 

  3. Sawicki T et al (2021) A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers 13(9):2025. https://doi.org/10.3390/cancers13092025

    Article  CAS  Google Scholar 

  4. Sargent D et al (2009) Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol 27(6):872. https://doi.org/10.1200/JCO.2008.19.5362

    Article  Google Scholar 

  5. Shah MA et al (2016) Impact of patient factors on recurrence risk and time dependency of oxaliplatin benefit in patients with colon cancer: analysis from modern-era adjuvant studies in the adjuvant colon cancer end points (ACCENT) database. J Clin Oncol 34(8):843. https://doi.org/10.1200/JCO.2015.63.0558

    Article  CAS  Google Scholar 

  6. Lee CS, Ryan EJ, Doherty GA (2014) Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: the role of inflammation. World J Gastroenterol: WJG 20(14):3751. https://doi.org/10.3748/wjg.v20.i14.3751

    Article  CAS  Google Scholar 

  7. Jurj A et al (2017) The new era of nanotechnology, an alternative to change cancer treatment. Drug Des Dev Ther 11:2871. https://doi.org/10.2147/DDDT.S142337

    Article  CAS  Google Scholar 

  8. Tang F, Li L, Chen D (2012) Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater 24(12):1504–1534. https://doi.org/10.1002/adma.201104763

    Article  CAS  Google Scholar 

  9. Vivero-Escoto JL et al (2010) Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small 6(18):1952–1967. https://doi.org/10.1002/smll.200901789

    Article  CAS  Google Scholar 

  10. Rajani C et al (2020) Cancer-targeted chemotherapy: emerging role of the folate anchored dendrimer as drug delivery nanocarrier. Pharmaceutical applications of dendrimers. Elsevier, London, pp 151–198. https://doi.org/10.3390/molecules25173982

    Chapter  Google Scholar 

  11. Tamanoi F (2018) Mesoporous slica-based nanomaterials and biomedical applications-part A. Academic Press

    Google Scholar 

  12. Ali I et al (2013) Platinum compounds: a hope for future cancer chemotherapy. Anticancer Agents Med Chem 13(2):296–306. https://doi.org/10.2174/1871520611313020016

    Article  CAS  Google Scholar 

  13. Sastry J, Kellie SJ (2005) Severe neurotoxicity, ototoxicity and nephrotoxicity following high-dose cisplatin and amifostine. Pediatr Hematol Oncol 22(5):441–445. https://doi.org/10.1080/08880010590964381

    Article  CAS  Google Scholar 

  14. Duan X et al (2016) Nanoparticle formulations of cisplatin for cancer therapy. Wiley Interdisc Rev: Nanomed Nanobiotechnol 8(5):776–791. https://doi.org/10.1002/wnan.1390

    Article  CAS  Google Scholar 

  15. Vivero-Escoto JL, Elnagheeb M (2015) Mesoporous silica nanoparticles loaded with cisplatin and phthalocyanine for combination chemotherapy and photodynamic therapy in vitro. Nanomaterials 5(4):2302–2316. https://doi.org/10.3390/nano5042302

    Article  CAS  Google Scholar 

  16. Varache M et al (2019) Loading of cisplatin into mesoporous silica nanoparticles: Effect of surface functionalization. Langmuir 35(27):8984–8995. https://doi.org/10.1021/acs.langmuir.9b00954

    Article  CAS  Google Scholar 

  17. Vallet-Regí M et al (2017) Mesoporous silica nanoparticles for drug delivery: Current insights. Molecules 23(1):47. https://doi.org/10.3390/molecules23010047

    Article  CAS  Google Scholar 

  18. Moodley T, Singh M (2019) Polymeric mesoporous silica nanoparticles for enhanced delivery of 5-fluorouracil in vitro. Pharmaceutics 11(6):288. https://doi.org/10.3390/pharmaceutics11060288

    Article  CAS  Google Scholar 

  19. Alipoor FJ, Asadi MH, Torkzadeh-Mahani M (2018) MIAT lncRNA is overexpressed in breast cancer and its inhibition triggers senescence and G1 arrest in MCF7 cell line. J Cell Biochem 119(8):6470–6481. https://doi.org/10.1002/jcb.26678

    Article  CAS  Google Scholar 

  20. Vickers NJ (2017) Animal communication: when I’m calling you, will you answer too? Curr Biol 27(14):R713–R715. https://doi.org/10.1016/j.cub.2017.05.064

    Article  CAS  Google Scholar 

  21. Martínez-Carmona M, Colilla M, Vallet-Regí M (2015) Smart mesoporous nanomaterials for antitumor therapy. Nanomaterials 5(4):1906–1937. https://doi.org/10.3390/nano5041906

    Article  CAS  Google Scholar 

  22. Castillo RR, Colilla M, Vallet-Regí M (2017) Advances in mesoporous silica-based nanocarriers for co-delivery and combination therapy against cancer. Expert Opin Drug Deliv 14(2):229–243. https://doi.org/10.1080/17425247.2016.1211637

    Article  CAS  Google Scholar 

  23. Vallet-Regí M, Colilla M, González B (2011) Medical applications of organic–inorganic hybrid materials within the field of silica-based bioceramics. Chem Soc Rev 40(2):596–607. https://doi.org/10.1039/C0CS00025F

    Article  Google Scholar 

  24. Lu J et al (2010) Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. Small 6(16):1794–1805. https://doi.org/10.1002/smll.201000538

    Article  CAS  Google Scholar 

  25. Tao Z et al (2008) Mesoporous silica nanoparticles inhibit cellular respiration. Nano Lett 8(5):1517–1526. https://doi.org/10.1021/nl080250u

    Article  CAS  Google Scholar 

  26. Raval N et al (2019) Importance of physicochemical characterization of nanoparticles in pharmaceutical product development. Basic fundamentals of drug delivery. Elsevier, pp 369–400. https://doi.org/10.1016/B978-0-12-817909-3.00010-8

    Chapter  Google Scholar 

  27. Liu W et al (2018) Galactosylated chitosan-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery. Royal Soc Open Sci 5(12):181027. https://doi.org/10.1098/rsos.181027

    Article  CAS  Google Scholar 

  28. Dasari S, Tchounwou PB (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 740:364–378. https://doi.org/10.1016/j.ejphar.2014.07.025

    Article  CAS  Google Scholar 

  29. Gao Y et al (2011) Controlled intracellular release of doxorubicin in multidrug-resistant cancer cells by tuning the shell-pore sizes of mesoporous silica nanoparticles. ACS Nano 5(12):9788–9798. https://doi.org/10.1021/nn2033105

    Article  CAS  Google Scholar 

  30. Lu J et al (2007) Mesoporous silica nanoparticles as a delivery system for hydrophobic anticancer drugs. Small 3(8):1341–1346

    Article  CAS  Google Scholar 

  31. Khosravian P et al (2016) Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel. Onco Targets Ther 9:7315. https://doi.org/10.2147/OTT.S113815

    Article  CAS  Google Scholar 

  32. Campbell KJ, Tait SW (2018) Targeting BCL-2 regulated apoptosis in cancer. Open Biol 8(5):180002. https://doi.org/10.1098/rsob.180002

    Article  CAS  Google Scholar 

  33. Brentnall M et al (2013) Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol 14(1):1–9. https://doi.org/10.1186/1471-2121-14-32

    Article  CAS  Google Scholar 

  34. Uhlmann S et al (2012) Global microRNA level regulation of EGFR-driven cell-cycle protein network in breast cancer. Mol Syst Biol 8(1):570. https://doi.org/10.1038/msb.2011.100

    Article  CAS  Google Scholar 

  35. Decock J et al (2011) Matrix metalloproteinases: protective roles in cancer. J Cell Mol Med 15(6):1254–1265. https://doi.org/10.1111/j.1582-4934.2011.01302.x

    Article  CAS  Google Scholar 

  36. Sharifi S, Dalir Abdolahinia E, Ghavimi MA, Dizaj SM, Aschner M, Saso L, Khan H (2022) Effect of Curcumin-Loaded Mesoporous Silica Nanoparticles on the Head and Neck Cancer Cell Line, HN5. Curr Issues Mol Biol 44(11):5247-5259. https://doi.org/10.3390/cimb44110357

  37. Krętowski R et al (2017) The effects of silica nanoparticles on apoptosis and autophagy of glioblastoma cell lines. Nanomaterials 7(8):230. https://doi.org/10.3390/nano7080230

    Article  CAS  Google Scholar 

  38. Sancho-Martínez SM et al (2011) Necrotic concentrations of cisplatin activate the apoptotic machinery but inhibit effector caspases and interfere with the execution of apoptosis. Toxicol Sci 122(1):73–85. https://doi.org/10.1093/toxsci/kfr098

    Article  CAS  Google Scholar 

  39. Zhou Y et al (2018) Mesoporous silica nanoparticles for drug and gene delivery. Acta pharmaceutica sinica B 8(2):165–177. https://doi.org/10.1016/j.apsb.2018.01.007

    Article  Google Scholar 

  40. Mishra S et al (2020) Folic acid-conjugated magnetic mesoporous silica nanoparticles loaded with quercetin: a theranostic approach for cancer management. RSC Adv 10(39):23148–23164. https://doi.org/10.1039/D0RA00664E

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The statements made herein are solely the responsibility of the authors. The author, Hirad Sinafar would like to acknowledge Research Assistant of Islamic Azad University Parand Branch due to the support granted through the Graduate Research Assistantship Program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vahid Naseh.

Ethics declarations

Declarations

As Corresponding Author, I confirm that the manuscript has been read and approved for submission by all the named authors.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

We declare that this manuscript is original, has not been published before, and is not currently being considered for publication elsewhere.

.

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

Sinafar, H., Noorbazargan, H., Tafvizi, F. et al. Evaluation of apoptotic and anti-metastatic effects by modified mesoporous silica nanoparticles (MSNs) with Zn and NH2 containing cisplatin on HT-29 cell line. J Nanopart Res 25, 89 (2023). https://doi.org/10.1007/s11051-023-05729-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-023-05729-y

Keywords

Navigation