Skip to main content
SpringerLink
Log in

In Vivo and In Vitro Biocompatibility Study of CuS Nanoparticles: Photosensitizer for Glioblastoma Photothermal Therapy

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Although photothermal treatment (PTT) has made significant progress in the fight against cancer, certain types of malignant tumors are still difficult to eradicate. PTT uses photothermal transforming agents to absorb NIR light and convert it to thermal energy, causing cancer cell death. In this study, we synthesized alginate (Alg)-coated CuS nanoparticles (CuS@Alg) as photothermal transforming agents to kill glioblastoma cancer cells. Nanoparticles were synthesized via a facile method, then, were characterized with different techniques such as ultraviolet–visible spectroscopy (UV–Vis), Fourier transform infrared (FTIR), X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Nanoparticles show high stability, and are monodisperse. CuS@Alg was discovered to have a spherical shape, a hydrodynamic size of about 19.93 nm, and a zeta potential of − 9.74 mV. CuS@Alg is able to increase temperature of medium under NIR light. Importantly, in vitro investigations show that PTT based on CuS@Alg has a strong theraputic impact, resulting in much high effectiveness. The LD50 and histopathology assays were used to confirm the NPs’ non-toxicity in vivo. Results from an in vivo subacute toxicity investigation showed that the fabricated NPs were perfectly safe to biomedical usage.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

Data Availability

The raw/processed data required to reproduce these findings cannot be shared at the moment, as the data also forms part of an ongoing study.

References

  1. Wirsching, H-G., & Weller, M. (2017). Glioblastoma. Malignant Brain Tumors, 265–288.

  2. Ohgaki, H., & Kleihues, P. (2013). The definition of primary and secondary glioblastoma. Clinical Cancer Research, 19(4), 764–772.

    Article  CAS  PubMed  Google Scholar 

  3. Philips, A., Henshaw, D. L., Lamburn, G., & O’Carroll, M. J. (2018) Brain tumours: rise in glioblastoma multiforme incidence in England 1995–2015 suggests an adverse environmental or lifestyle factor. Journal of Environmental and Public Health, 2018

  4. Alexander, B. M., Ba, S., Berger, M. S., Berry, D. A., Cavenee, W. K., Chang, S. M., et al. (2018). Adaptive global innovative learning environment for glioblastoma: GBM AGILE. Clinical Cancer Research, 24(4), 737–743.

  5. Yang, P., Zhang, W., Wang, Y., Peng, X., Chen, B., Qiu, X., et al. (2015). IDH mutation and MGMT promoter methylation in glioblastoma: results of a prospective registry. Oncotarget, 6(38), 40896.

  6. Oldrini, B., Vaquero-Siguero, N., Mu, Q., Kroon, P., Zhang, Y., Galán-Ganga,  et al. (2020). MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas. Nature Communications, 11(1), 1–10.

  7. Islam, R., Isaacson, B. J., Zickerman, P. M., Ratanawong, C., & Tipping, S. J. (2002). Hemorrhagic cystitis as an unexpected adverse reaction to temozolomide: case report. American Journal of Clinical Oncology, 25(5), 513–514.

    Article  PubMed  Google Scholar 

  8. Mahmoudi, K., Garvey, K., Bouras, A., Cramer, G., Stepp, H., Jesu Raj, J., et al. (2019). Hadjipanayis, 5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas. Journal of Neuro-Oncology, 141(3), 595–607.

  9. Cramer, S. W., & Chen, C. C. (2020). Photodynamic therapy for the treatment of glioblastoma. Frontiers in Surgery, 6, 81.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Greish, K. (2010) Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting, Cancer nanotechnology, Springer, pp. 25–37.

  11. Kumar, A. V. P., Dubey, S. K., Tiwari, S., Puri, A., Hejmady, S., Gorain, B., & Kesharwani, P. (2021). Kesharwani, Recent advances in nanoparticles mediated photothermal therapy induced tumor regression. International Journal of Pharmaceutics, 606:120848.

  12. Jaque, D., Maestro, L. M., del Rosal, B., Haro-Gonzalez, P., Benayas, A., Plaza, J., et al. (2014). Nanoparticles for photothermal therapies. Nanoscale, 6(16), 9494–9530.

  13. Lucky, S. S., Soo, K. C., & Zhang, Y. (2015). Nanoparticles in Photodynamic Therapy. Chemical Reviews, 115(4), 1990–2042.

    Article  CAS  PubMed  Google Scholar 

  14. Bastiancich, C., Da Silva, A., & Esteve, M-A. (2021). Photothermal therapy for the treatment of glioblastoma: potential and preclinical challenges. Frontiers in Oncology, 3095.

  15. Sivasubramanian, M., Chuang, Y. C., & Lo, L.-W. (2019). Evolution of nanoparticle-mediated photodynamic therapy: from superficial to deep-seated cancers. Molecules, 24(3), 520.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gargioni, C., Borzenkov, M., D’Alfonso, L., Sperandeo, P., Polissi, A., Cucca, L., et al.(2020). Self-assembled monolayers of copper sulfide nanoparticles on glass as antibacterial coatings. Nanomaterials, 10(2), 352.

  17. Tapiero, H., Townsend, D., & á., Tew, K. (2003). Trace elements in human physiology and pathology. Copper, Biomedicine & Pharmacotherapy, 57(9), 386–398.

  18. Wang, S., Riedinger, A., Li, H., Fu, C., Liu, H., Li, L., et al. (2015). Plasmonic copper sulfide nanocrystals exhibiting near-infrared photothermal and photodynamic therapeutic effects. ACS Nano, 9(2), 1788–1800.

  19. Jaiser, S. R., & Winston, G. P. (2010). Winston, Copper deficiency myelopathy. Journal of Neurology, 257(6), 869–881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lin, R. K., Chiu, C. I., Hsu, C. H., Lai, Y. J., Venkatesan, P., Huang, P. H.,  et al. (2018). Photocytotoxic copper (II) complexes with schiff‐base scaffolds for photodynamic therapy. Chemistry–A European Journal, 24(16), 4111–4120.

  21. Morgese, G., Shirmardi Shaghasemi, B., Causin, V., Zenobi‐Wong, M., Ramakrishna, S. N., Reimhult, E., & Benetti, E. M. (2017). Next‐generation polymer shells for inorganic nanoparticles are highly compact, ultra‐dense, and long‐lasting cyclic brushes. Angewandte Chemie, 129(16), 4578–4582.

  22. Wang, C., Yokota, T., & Someya, T. (2021). Natural biopolymer-based biocompatible conductors for stretchable bioelectronics. Chemical Reviews, 121(4), 2109–2146.

    Article  CAS  PubMed  Google Scholar 

  23. Sanchez-Ballester, N. M., Bataille, B., & Soulairol, I. (2021). Sodium alginate and alginic acid as pharmaceutical excipients for tablet formulation: Structure-function relationship. Carbohydrate Polymers, 270, 118399.

  24. Varghese, R. J., Parani, S., Remya, V., Maluleke, R., Thomas, S., & Oluwafemi, O. S. (2020). Sodium alginate passivated CuInS2/ZnS QDs encapsulated in the mesoporous channels of amine modified SBA 15 with excellent photostability and biocompatibility. International Journal of Biological Macromolecules, 161, 1470–1476.

  25. Neshastehriz, A., Khateri, M., Ghaznavi, H., & Shakeri-Zadeh, A. (2018). Investigating the therapeutic effects of alginate nanogel co-loaded with gold nanoparticles and cisplatin on U87-MG human glioblastoma cells. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 18(6), 882–890.

  26. Nosrati, H., Seidi, F., Hosseinmirzaei, A., Mousazadeh, N., Mohammadi, A., Ghaffarlou, M.,  et al. (2022). Prodrug polymeric nanoconjugates encapsulating gold nanoparticles for enhanced X‐Ray radiation therapy in breast cancer. Advanced Healthcare Materials, 11(3), 2102321.

  27. Leroux, G., Neumann, M., Meunier, C.F., Voisin, V., Habsch, I., Caron, N., et al. (2021). Alginate@ TiO2 hybrid microcapsules with high in vivo biocompatibility and stability for cell therapy. Colloids and Surfaces B: Biointerfaces, 203, 111770.

  28. Feng, L., Wu, S., & Wu, Y. (2021). Intracellular Bottom‐up Synthesis of Ultrasmall CuS Nanodots in Cancer Cells for Simultaneous Photothermal Therapy and COX‐2 Inactivation. Advanced Functional Materials, 31(27), 2101297.

  29. Shi, H., Yan, R., Wu, L., Sun, Y., Liu, S., Zhou, Z. He, J., & Ye, D. (2018). Tumor-targeting CuS nanoparticles for multimodal imaging and guided photothermal therapy of lymph node metastasis. Acta Biomaterialia, 72, 256–265.

  30. Zhang, C., Fu, Y.-Y., Zhang, X., Yu, C., Zhao, Y., & Sun, S.-K. (2015). BSA-directed synthesis of CuS nanoparticles as a biocompatible photothermal agent for tumor ablation in vivo. Dalton Transactions, 44(29), 13112–13118.

  31. Zhao, J., Yang, G., Zhang, Y., Zhang, S., & Zhang, P. (2019). A simple preparation of HDA-CuS nanoparticles and their tribological properties as a water-based lubrication additive. Tribology Letters, 67(3), 1–11.

    Article  Google Scholar 

  32. Han, J., Zhou, Z., Yin, R., Yang, D., & Nie, J. (2010). Alginate–chitosan/hydroxyapatite polyelectrolyte complex porous scaffolds: Preparation and characterization. International Journal of Biological Macromolecules, 46(2), 199–205.

  33. Pongjanyakul, T. (2009). Alginate–magnesium aluminum silicate films: importance of alginate block structures. International Journal of Pharmaceutics, 365(1-2), 100–108.

  34. Sarmento, B., Ferreira, D., Veiga, F., & Ribeiro, A. (2006). Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies. Carbohydrate Polymers, 66(1), 1–7.

    Article  CAS  Google Scholar 

  35. Pereira, R., Tojeira, A., Vaz, D. C., Mendes, A., & Bártolo, P. (2011). Preparation and characterization of films based on alginate and aloe vera. International Journal of Polymer Analysis and Characterization, 16(7), 449–464.

    Article  CAS  Google Scholar 

  36. Beishenaliev, A., Faruqu, F. N., Leo, B. F., Lit, L. C., Loke, Y. L., Chang, C.-C., et al. (2021). Facile synthesis of biocompatible sub-5 nm alginate-stabilised gold nanoparticles with sonosensitising properties.  Colloids and Surfaces A: Physicochemical and Engineering Aspects, 627, 127141.

Download references

Funding

This work was supported by the Xi’an Children’s Hospital.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Zhen’an Hospital, Shangluo, 711500, China

    Yin Li

  2. Department of Neurosurgery, Xi’an Children’s Hospital, Xi’an, 710000, China

    Zhangkai Yang

  3. Medical Laboratory Techniques Department, Al-Mustaqbal University College, Babylon, Hilla, 51001, Iraq

    Abduladheem Turki Jalil

  4. Department of Biophysics, College of Applied Sciences, University of Anbar, Ramadi, Iraq

    Marwan Mahmood Saleh

  5. Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq

    Marwan Mahmood Saleh

  6. Department of Outpatient Comprehensive Surgery, Xi’an Children’s Hospital, Xi’an, 710000, China

    Bin Wu

Authors
  1. Yin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhangkai Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abduladheem Turki Jalil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marwan Mahmood Saleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Yin Li: conceptualization, methodology, software, formal analysis, investigation, and writing—original draft. Zhangkai Yang: investigation and software. Abduladheem Turki Jalil: investigation. Marwan Mahmood Saleh: investigation and Methodology. Bin Wu: conceptualization and writing—original draft.

Corresponding author

Correspondence to Bin Wu.

Ethics declarations

Ethical Approval

This study was approved by the Ethics Committee of the Xi’an Children’s Hospital.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

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.

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

Li, Y., Yang, Z., Jalil, A.T. et al. In Vivo and In Vitro Biocompatibility Study of CuS Nanoparticles: Photosensitizer for Glioblastoma Photothermal Therapy. Appl Biochem Biotechnol 195, 4084–4095 (2023). https://doi.org/10.1007/s12010-023-04313-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-023-04313-3

Keywords

Search

Navigation