Publication detail

Surface-PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticine

TESAŘOVÁ, B. DOSTÁLOVÁ, S. ŠMÍDOVÁ, V. GOLIÁŠOVÁ, Z. ŠKUBALOVÁ, Z. MICHÁLKOVÁ, H. HYNEK, D. MICHÁLEK, P. POLANSKÁ, H. VACULOVIČOVÁ, M. HÁČEK, J. ECKSCHLAGER, T. STIBOROVÁ, M. PIRE, A.S. NEVES, A.R.M. ABRANTES, A.M. RODRIGUES, T. MATAFOME, P. BOTELHO, M.F. TEIXEIRA, P. MENDES, F. HEGER, Z.

Original Title

Surface-PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticine

Type

journal article in Web of Science

Language

English

Original Abstract

Surface functionalisations substantially influence the performance of drug delivery vehicles by improving their biocompatibility, selectivity and circulation in bloodstream. Herein, we present the study of in vitro and in vivo behaviour of a highly potent cytostatic alkaloid ellipticine (Elli) encapsulated in internal cavity of ferritin (FRT)-based nanocarrier (hereinafter referred to as FRTElli). In addition, FRTElli surface was functionalised with three different molecular coatings: two types of protective PAS peptides (10- or 20-residues lengths) with sequences comprising amino acids proline (P), alanine (A) and serine (S) (to form PAS-10-FRTElli or PAS-20-FRTElli, respectively), or polyethylene glycol (PEG-FRTElli). All three surface modifications of FRT disposed sufficient encapsulation efficiency of Elli with no premature cumulative release of cargo. Noteworthy, all tested surface modifications displayed beneficial effects on the in vitro biocompatibility. PAS-10-FRTElli exhibited markedly reduced uptake by macrophages compared to PAS-20-FRTElli, PEG-FRTElli or unmodified FRTElli. The exceptional properties of PAS-10-FRTElli were validated by an array of in vitro analyses including formation of protein corona, uptake efficiency or screenings of selectivity of cytotoxicity. In murine preclinical model bearing triple -negative breast cancer (MDA-MB-231) xenograft, compared to free Elli or FRTElli, PAS-10-FRTElli displayed enhanced accumulation of Elli within tumour tissue, while hampering the uptake of Elli into off-target tissues. Noteworthy, PAS-10-FRTElli led to decreased in vivo complement (C3) activation and protein corona formation. Taken together, presented in vivo results indicate that PAS-10-FRTElli represents a promising stealth platform for translation into clinical settings.

Keywords

Biocompatibility; Breast carcinoma; Cancer therapy; Ferritin; PASylation; PEGylation

Authors

TESAŘOVÁ, B.; DOSTÁLOVÁ, S.; ŠMÍDOVÁ, V.; GOLIÁŠOVÁ, Z.; ŠKUBALOVÁ, Z.; MICHÁLKOVÁ, H.; HYNEK, D.; MICHÁLEK, P.; POLANSKÁ, H.; VACULOVIČOVÁ, M.; HÁČEK, J.; ECKSCHLAGER, T.; STIBOROVÁ, M.; PIRE, A.S.; NEVES, A.R.M.; ABRANTES, A.M.; RODRIGUES, T.; MATAFOME, P.; BOTELHO, M.F.; TEIXEIRA, P.; MENDES, F.; HEGER, Z.

Released

31. 3. 2020

ISBN

2352-9407

Periodical

Applied Materials Today

Year of study

18

Number

UNSP 100501

State

Kingdom of the Netherlands

Pages from

1

Pages to

11

Pages count

11

URL

https://doi.org/10.1016/j.apmt.2019.100501

BibTex

@article{BUT164291,
  author="TESAŘOVÁ, B. and DOSTÁLOVÁ, S. and ŠMÍDOVÁ, V. and GOLIÁŠOVÁ, Z. and ŠKUBALOVÁ, Z. and MICHÁLKOVÁ, H. and HYNEK, D. and MICHÁLEK, P. and POLANSKÁ, H. and VACULOVIČOVÁ, M. and HÁČEK, J. and ECKSCHLAGER, T. and STIBOROVÁ, M. and PIRE, A.S. and NEVES, A.R.M. and ABRANTES, A.M. and RODRIGUES, T. and MATAFOME, P. and BOTELHO, M.F. and TEIXEIRA, P. and MENDES, F. and HEGER, Z.",
  title="Surface-PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticine",
  journal="Applied Materials Today",
  year="2020",
  volume="18",
  number="UNSP 100501",
  pages="1--11",
  doi="10.1016/j.apmt.2019.100501",
  issn="2352-9407",
  url="https://doi.org/10.1016/j.apmt.2019.100501"
}