Publication detail

Conotoxin-derived biomimetic coiled cone-shaped peptide as ligand for selective nanodelivery to norepinephrine transporter-expressing neuroblastoma cells

ŽIVOTSKÁ, H. MOKRÝ, M. MERLOS RODRIGO, M. MICHÁLKOVÁ, H. KAPOLKOVÁ, K. ŠPLÍCHAL, Z. STOKOWA-SOLTYS, K. MILOSAVLJEVIĆ, V. GURÁŇ, R. RICHTERA, L. HADDAD, Y. REX, S. HEGER, Z.

Original Title

Conotoxin-derived biomimetic coiled cone-shaped peptide as ligand for selective nanodelivery to norepinephrine transporter-expressing neuroblastoma cells

Type

journal article in Web of Science

Language

English

Original Abstract

Selective drug delivery is an emerging powerful strategy, which promises efficient and safer neuroblastoma treatment in contrast to conventional therapeutic modalities. Herein, we present a newly designed apoferritin nanovehicle loaded with ellipticine and decorated with conotoxin-derived biomimetic peptide YKL-6 (sequence: YKLYKLYKLYKLYKLYKLC) to target the norepinephrine transporter (hNET), which is highly expressed on neuroblastoma cells membrane. The peptide forms a coiled cone-shape forming anti-parallel beta sheets in aggregation in vitro. Molecular docking analysis suggests electrostatic interaction mediated by lysine residues against negatively charged residues of the hNET. The assembled nanovehicles show optimal biocompatibility in healthy epithelial cells and ability to deliver ellipticine into neuroblastoma cells (UKF-NB-4 and SH-SY5Y). In our analyses, we have excluded hNET-mediated endocytosis as an uptake mechanism and demonstrated the ellipticine-triggered anti-proliferative mechanisms in neuroblastoma cells via downregulation of Bcl-2, survivin and N-myc. Finally, we present a selective inhibition of neuroblastoma growth and metastasis in vivo in an ex ovo and in ovo chicken chorioallantoic membrane assay. Overall, these findings demonstrate a great leap forward in the design of biomimetic homing peptides towards possible application in neuroblastoma nanomedicine.

Keywords

Apoferritin; Biomimetic peptides; Drug delivery; Neuroblastoma; Norepinephrine transporter; Targeted therapy

Authors

ŽIVOTSKÁ, H.; MOKRÝ, M.; MERLOS RODRIGO, M.; MICHÁLKOVÁ, H.; KAPOLKOVÁ, K.; ŠPLÍCHAL, Z.; STOKOWA-SOLTYS, K.; MILOSAVLJEVIĆ, V.; GURÁŇ, R.; RICHTERA, L.; HADDAD, Y.; REX, S.; HEGER, Z.

Released

1. 6. 2022

ISBN

2352-9407

Periodical

Applied Materials Today

Year of study

27

Number

101410

State

Kingdom of the Netherlands

Pages from

1

Pages to

14

Pages count

14

URL

https://doi.org/10.1016/j.apmt.2022.101410

BibTex

@article{BUT177479,
  author="ŽIVOTSKÁ, H. and MOKRÝ, M. and MERLOS RODRIGO, M. and MICHÁLKOVÁ, H. and KAPOLKOVÁ, K. and ŠPLÍCHAL, Z. and STOKOWA-SOLTYS, K. and MILOSAVLJEVIĆ, V. and GURÁŇ, R. and RICHTERA, L. and HADDAD, Y. and REX, S. and HEGER, Z.",
  title="Conotoxin-derived biomimetic coiled cone-shaped peptide as ligand for selective nanodelivery to norepinephrine transporter-expressing neuroblastoma cells",
  journal="Applied Materials Today",
  year="2022",
  volume="27",
  number="101410",
  pages="1--14",
  doi="10.1016/j.apmt.2022.101410",
  issn="2352-9407",
  url="https://doi.org/10.1016/j.apmt.2022.101410"
}