J 2020

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

TESAROVA, B., S. DOSTALOVA, V. SMIDOVA, Zita GOLIÁŠOVÁ, Z. SKUBALOVA et. al.

Basic information

Original name

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

Authors

TESAROVA, B. (203 Czech Republic), S. DOSTALOVA (203 Czech Republic), V. SMIDOVA (203 Czech Republic), Zita GOLIÁŠOVÁ (203 Czech Republic), Z. SKUBALOVA (203 Czech Republic), H. MICHALKOVA (203 Czech Republic), H. DAVID (203 Czech Republic), P. MICHALEK (203 Czech Republic), Hana POLANSKÁ (203 Czech Republic, belonging to the institution), M. VACUOVICOVA (203 Czech Republic), J. HACEK (203 Czech Republic), T. ECKSCHLAGER (203 Czech Republic), M. STIBOROVA (203 Czech Republic), A. S. PIRES (620 Portugal), A. R. M. NEVES (620 Portugal), A. M. ABRANTES (620 Portugal), T. RODRIGUES (620 Portugal), P. MATAFOME (620 Portugal), M. F. BOTELHO (620 Portugal), P. TEIXEIRA (620 Portugal), F. MENDES (620 Portugal) and Z. HEGER (203 Czech Republic, guarantor)

Edition

APPLIED MATERIALS TODAY, AMSTERDAM, ELSEVIER SCIENCE BV, 2020, 2352-9407

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30404 Biomaterials

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 10.041

RIV identification code

RIV/00216224:14110/20:00115972

Organization unit

Faculty of Medicine

UT WoS

000530652300014

Keywords in English

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

Tags

International impact, Reviewed
Změněno: 7/10/2021 17:13, Mgr. Tereza Miškechová

Abstract

V originále

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. (C) 2019 Elsevier Ltd. All rights reserved.

Links

LQ1601, research and development project
Name: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR