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KRAUSOVÁ, K. CHAROUSOVÁ, M. KRATOCHVÍL, Z. TAKÁCSOVÁ, P. TESAŘOVÁ, B. SIVÁK, L. PEŠKOVÁ, M. SÚKUPOVÁ, M. ŽIVOTSKÁ, H. MAKOVICKÝ, P. YAMASHITA, I. OKAMOTO, N. HYNEK, D. HADDAD, Y. PEKAŘÍK, V. REX, S. HEGER, Z.
Original Title
Toward understanding the kinetics of disassembly of ferritins of varying origin and subunit composition
Type
journal article in Web of Science
Language
English
Original Abstract
Understanding the reversible reassembly properties of ferritins (FRTs) is crucial for enabling their applicability in nanomedicine. These properties include drug loading capabilities and also subsequent payload release in desired site-of-action. Thus, the presented study is focused on understanding the disassembly of recombinantly produced FRTs of varying origin and subunit composition, i.e. equine FRT composed of 22 L- and 2 H-subunits (EcaLH) or 24 L-subunits (EcaL), human FRT composed of 24 H-subunits (HsaH) and archaeal Pyrococcus furiosus FRT (Pfu). Disassembly was distinctly influenced by pH and ionic strength. Except for Pfu, the disassembly kinetics in acidic pH is rapid upon reaching an innate threshold, reaching the final state within minutes. Disassembly kinetics in basic pH is slower. Pfu is partially disassembled within the entire pH range. While equine FRT disassembles into free subunits, HsaH disassembles into subunit clusters. EcaL and Pfu form large aggregates during disassembly in mildly acidic pH, although basic pH causes partial disassembly without aggregation, suggesting usability for basic pH-triggered drug loading. We show that in human serum/plasma, FRTs readily form protein corona, hampering their uptake. Interestingly, we found out that archaeal Pfu likely exhibits similar receptor affinity as mammalian FRTs. Further, in vivo toxicity and biodistribution study of a single dose of FRTs demonstrated very low toxicity of FRTs and their preferential liver/kidney bioaccumulation.
Keywords
Archaeal ferritin; Continuous multimodal nanoparticle size; analysis; Mammalian ferritin; Native PAGE; Protein corona
Authors
KRAUSOVÁ, K.; CHAROUSOVÁ, M.; KRATOCHVÍL, Z.; TAKÁCSOVÁ, P.; TESAŘOVÁ, B.; SIVÁK, L.; PEŠKOVÁ, M.; SÚKUPOVÁ, M.; ŽIVOTSKÁ, H.; MAKOVICKÝ, P.; YAMASHITA, I.; OKAMOTO, N.; HYNEK, D.; HADDAD, Y.; PEKAŘÍK, V.; REX, S.; HEGER, Z.
Released
31. 8. 2022
ISBN
2352-9407
Periodical
Applied Materials Today
Year of study
28
Number
101535
State
Kingdom of the Netherlands
Pages from
1
Pages to
12
Pages count
URL
https://doi.org/10.1016/j.apmt.2022.101535
BibTex
@article{BUT179433, author="KRAUSOVÁ, K. and CHAROUSOVÁ, M. and KRATOCHVÍL, Z. and TAKÁCSOVÁ, P. and TESAŘOVÁ, B. and SIVÁK, L. and PEŠKOVÁ, M. and SÚKUPOVÁ, M. and ŽIVOTSKÁ, H. and MAKOVICKÝ, P. and YAMASHITA, I. and OKAMOTO, N. and HYNEK, D. and HADDAD, Y. and PEKAŘÍK, V. and REX, S. and HEGER, Z.", title="Toward understanding the kinetics of disassembly of ferritins of varying origin and subunit composition", journal="Applied Materials Today", year="2022", volume="28", number="101535", pages="1--12", doi="10.1016/j.apmt.2022.101535", issn="2352-9407", url="https://doi.org/10.1016/j.apmt.2022.101535" }