Boron nitride nanotube-CREKA peptide as an effective target system to metastatic breast cancer

Abstract

Purpose

The development of nanomaterials that are capable of recognizing disease-specific biomarkers with high sensitivity and specificity is related to several advances in the field of nanomedicine. Furthermore, the targeted delivery of anticancer agents to tumor tissues enhances their efficiency and reduces their toxic side effects. Boron nitride nanotubes (BNNTs) are nanostructured materials, analog to carbon nanotubes, which present good biocompatibility and morphology suitable for tumor cell internalization. CREKA is a pentapeptide that has a high affinity to fibrin, a protein found in the new tumor vessels in the early stages of metastasis and in thrombosis regions.

Methods

In this study BNNTs were chemically functionalized with the peptide CREKA, and this system was characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), zeta potential, scanning electron microscopy, and transmission electron microscopy.

Results

After the mentioned chemical steps, the FTIR analysis shows an organic phase related to the CREKA, TGA indicates that about 10% of the peptide is firmly attached to BNNT surface. In addition, the radiolabeling process was successful, achieving the purity required for the biodistribution study. In vivo experiments showed that a considerable amount of BNNT-CREKA was accumulated at the tumor and metastasis sites.

Conclusion

The present results indicate an effective targeting of the system to tumor and metastasis sites. Further studies can reveal potential applications of functionalized BNNTs in cancer treatment.

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Acknowledgements

The authors would like to thank FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for all financial support. ALBB, EMBS, JMR, LBF, THF and VNC acknowledge grants from CNPq. RSF and VMS acknowledge grants from CAPES. Experiments and analyses involving electron microscopy were performed in the Center of Microscopy at the Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil (http://www.microscopia.ufmg.br).

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Correspondence to Tiago Hilário Ferreira or Edésia Martins Barros de Sousa.

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All animal experimental protocols were approved by the Ethics Committee for Animal Experiments (CEUA) from Federal University of Minas Gerais under the protocol number 284/17 and comply with the requirements of the guide for the care and use of laboratory animals.

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Ferreira, T.H., de Oliveira Freitas, L.B., Fernandes, R.S. et al. Boron nitride nanotube-CREKA peptide as an effective target system to metastatic breast cancer. J. Pharm. Investig. 50, 469–480 (2020). https://doi.org/10.1007/s40005-019-00467-7

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Keywords

  • BNNT
  • CREKA peptide
  • 99mTc
  • Nanomedicine
  • Active target
  • In vivo assay
  • Metastasis