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@article{1670256, author = {Tesarova, B. and Dostalova, S. and Smidova, V. and Goliášová, Zita and Skubalova, Z. and Michalkova, H. and David, H. and Michalek, P. and Polanská, Hana and Vacuovicova, M. and Hacek, J. and Eckschlager, T. and Stiborova, M. and Pires, 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.}, article_location = {AMSTERDAM}, article_number = {MAR 2020}, doi = {http://dx.doi.org/10.1016/j.apmt.2019.100501}, keywords = {Biocompatibility; Breast carcinoma; Cancer therapy; Ferritin; PASylation; PEGylation}, language = {eng}, issn = {2352-9407}, journal = {APPLIED MATERIALS TODAY}, title = {Surface-PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticine}, url = {https://www.sciencedirect.com/science/article/pii/S2352940719306201?via%3Dihub}, volume = {18}, year = {2020} }
TY - JOUR ID - 1670256 AU - Tesarova, B. - Dostalova, S. - Smidova, V. - Goliášová, Zita - Skubalova, Z. - Michalkova, H. - David, H. - Michalek, P. - Polanská, Hana - Vacuovicova, M. - Hacek, J. - Eckschlager, T. - Stiborova, M. - Pires, A. S. - Neves, A. R. M. - Abrantes, A. M. - Rodrigues, T. - Matafome, P. - Botelho, M. F. - Teixeira, P. - Mendes, F. - Heger, Z. PY - 2020 TI - Surface-PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticine JF - APPLIED MATERIALS TODAY VL - 18 IS - MAR 2020 SP - 1-11 EP - 1-11 PB - ELSEVIER SCIENCE BV SN - 23529407 KW - Biocompatibility KW - Breast carcinoma KW - Cancer therapy KW - Ferritin KW - PASylation KW - PEGylation UR - https://www.sciencedirect.com/science/article/pii/S2352940719306201?via%3Dihub L2 - https://www.sciencedirect.com/science/article/pii/S2352940719306201?via%3Dihub N2 - 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. ER -
TESAROVA, B., S. DOSTALOVA, V. SMIDOVA, Zita GOLIÁŠOVÁ, Z. SKUBALOVA, H. MICHALKOVA, H. DAVID, P. MICHALEK, Hana POLANSKÁ, M. VACUOVICOVA, J. HACEK, T. ECKSCHLAGER, M. STIBOROVA, A. S. PIRES, A. R. M. NEVES, A. M. ABRANTES, T. RODRIGUES, P. MATAFOME, M. F. BOTELHO, P. TEIXEIRA, F. MENDES and Z. HEGER. Surface-PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticine. \textit{APPLIED MATERIALS TODAY}. AMSTERDAM: ELSEVIER SCIENCE BV, 2020, vol.~18, MAR 2020, p.~1-11. ISSN~2352-9407. Available from: https://dx.doi.org/10.1016/j.apmt.2019.100501.
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