Engineered human H-chain ferritin with reversed charge of the
internal cavity exhibits RNA-mediated spongelike effect for
loading RNA/DNA-binding molecules

J 2024

Engineered human H-chain ferritin with reversed charge of the internal cavity exhibits RNA-mediated spongelike effect for loading RNA/DNA-binding molecules

CHAROUSOVA, Marketa; Marie KUDLIČKOVÁ PEŠKOVÁ; Paulina TAKACSOVA; Katerina KAPOLKOVA; Yazan HADDAD et. al.

Základní údaje

Originální název

Engineered human H-chain ferritin with reversed charge of the internal cavity exhibits RNA-mediated spongelike effect for loading RNA/DNA-binding molecules

Autoři

CHAROUSOVA, Marketa; Marie KUDLIČKOVÁ PEŠKOVÁ; Paulina TAKACSOVA; Katerina KAPOLKOVA; Yazan HADDAD; Jan BILEK; Ladislav SIVAK; Tomáš BARTEJS; Zbynek HEGER a Vladimír PEKAŘÍK

Vydání

BIOMATERIALS SCIENCE, ENGLAND, ROYAL SOC CHEMISTRY, 2024, 2047-4830

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10400 1.4 Chemical sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.700

Kód RIV

RIV/00216224:14740/24:00138982

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1039/d3bm01257c

UT WoS

001147894000001

EID Scopus

2-s2.0-85182924190

Klíčová slova anglicky

DELIVERY-SYSTEM; NANOPARTICLES; APOFERRITIN; ENCAPSULATION; DOXORUBICIN; SOLUBILITY; NANOCAGE; SIRNA; NANOCLUSTERS; DEGRADATION

Štítky

CF CRYO, CF GEN, rivok

Změněno: 9. 6. 2025 13:54, Mgr. Eva Dubská

Anotace

V originále

Ferritins are globular proteins with an internal cavity that enables the encapsulation of a plethora of low-mass compounds. Unfortunately, the overall negative surface charge of ferritin's internal cavity hampers efficient loading of negatively charged molecules. Therefore, we produced a genetically engineered human H-chain ferritin containing a cationic RKRK domain, reversing the natural net charge of the cavity to positive, thus allowing for efficient encapsulation of negatively charged siRNA. Due to the reversed, positive charge mediated by RKRK domains, the recombinant ferritin produced in E. coli inherently carries a load of bacterial RNA inside its cavity, turning the protein into an effective sponge possessing high affinity for DNA/RNA-binding substances that can be loaded with markedly higher efficiency compared to the wildtype protein. Using doxorubicin as payload, we show that due to its loading through the RNA sponge, doxorubicin is released in a sustained manner, with a cytotoxicity profile similar to the free drug. In summary, this is the first report demonstrating a ferritin/nucleic acid hybrid delivery vehicle with a broad spectrum of properties exploitable in various fields of biomedical applications.

Návaznosti

EF18_046/0015974, projekt VaV

Název: Modernizace České infrastruktury pro integrativní strukturní biologii

90127, velká výzkumná infrastruktura

Název: CIISB II

90267, velká výzkumná infrastruktura

Název: NCMG III

Citovat

CHAROUSOVA, Marketa; Marie KUDLIČKOVÁ PEŠKOVÁ; Paulina TAKACSOVA; Katerina KAPOLKOVA; Yazan HADDAD; Jan BILEK; Ladislav SIVAK; Tomáš BARTEJS; Zbynek HEGER a Vladimír PEKAŘÍK. Engineered human H-chain ferritin with reversed charge of the internal cavity exhibits RNA-mediated spongelike effect for loading RNA/DNA-binding molecules. BIOMATERIALS SCIENCE. ENGLAND: ROYAL SOC CHEMISTRY, 2024, roč. 12, č. 5, s. 1249-1262. ISSN 2047-4830. Dostupné z: https://doi.org/10.1039/d3bm01257c.

@article{2481640,
   author = {Charousova, Marketa and Kudličková Pešková, Marie and Takacsova, Paulina and Kapolkova, Katerina and Haddad, Yazan and Bilek, Jan and Sivak, Ladislav and Bartejs, Tomáš and Heger, Zbynek and Pekařík, Vladimír},
   article_location = {ENGLAND},
   article_number = {5},
   doi = {https://doi.org/10.1039/d3bm01257c},
   keywords = {DELIVERY-SYSTEM; NANOPARTICLES; APOFERRITIN; ENCAPSULATION; DOXORUBICIN; SOLUBILITY; NANOCAGE; SIRNA; NANOCLUSTERS; DEGRADATION},
   language = {eng},
   issn = {2047-4830},
   journal = {BIOMATERIALS SCIENCE},
   title = {Engineered human H-chain ferritin with reversed charge of the internal cavity exhibits RNA-mediated spongelike effect for loading RNA/DNA-binding molecules},
   url = {https://pubs.rsc.org/en/content/articlelanding/2024/bm/d3bm01257c},
   volume = {12},
   year = {2024}
}

TY  - JOUR
ID  - 2481640
AU  - Charousova, Marketa - Kudličková Pešková, Marie - Takacsova, Paulina - Kapolkova, Katerina - Haddad, Yazan - Bilek, Jan - Sivak, Ladislav - Bartejs, Tomáš - Heger, Zbynek - Pekařík, Vladimír
PY  - 2024
TI  - Engineered human H-chain ferritin with reversed charge of the internal cavity exhibits RNA-mediated spongelike effect for loading RNA/DNA-binding molecules
JF  - BIOMATERIALS SCIENCE
VL  - 12
IS  - 5
SP  - 1249-1262
EP  - 1249-1262
PB  - ROYAL SOC CHEMISTRY
SN  - 20474830
KW  - DELIVERY-SYSTEM
KW  - NANOPARTICLES
KW  - APOFERRITIN
KW  - ENCAPSULATION
KW  - DOXORUBICIN
KW  - SOLUBILITY
KW  - NANOCAGE
KW  - SIRNA
KW  - NANOCLUSTERS
KW  - DEGRADATION
UR  - https://pubs.rsc.org/en/content/articlelanding/2024/bm/d3bm01257c
N2  - Ferritins are globular proteins with an internal cavity that enables the encapsulation of a plethora of low-mass compounds. Unfortunately, the overall negative surface charge of ferritin's internal cavity hampers efficient loading of negatively charged molecules. Therefore, we produced a genetically engineered human H-chain ferritin containing a cationic RKRK domain, reversing the natural net charge of the cavity to positive, thus allowing for efficient encapsulation of negatively charged siRNA. Due to the reversed, positive charge mediated by RKRK domains, the recombinant ferritin produced in E. coli inherently carries a load of bacterial RNA inside its cavity, turning the protein into an effective sponge possessing high affinity for DNA/RNA-binding substances that can be loaded with markedly higher efficiency compared to the wildtype protein. Using doxorubicin as payload, we show that due to its loading through the RNA sponge, doxorubicin is released in a sustained manner, with a cytotoxicity profile similar to the free drug. In summary, this is the first report demonstrating a ferritin/nucleic acid hybrid delivery vehicle with a broad spectrum of properties exploitable in various fields of biomedical applications.
ER  -

CHAROUSOVA, Marketa; Marie KUDLIČKOVÁ PEŠKOVÁ; Paulina TAKACSOVA; Katerina KAPOLKOVA; Yazan HADDAD; Jan BILEK; Ladislav SIVAK; Tomáš BARTEJS; Zbynek HEGER a Vladimír PEKAŘÍK. Engineered human H-chain ferritin with reversed charge of the internal cavity exhibits RNA-mediated spongelike effect for loading RNA/DNA-binding molecules. \textit{BIOMATERIALS SCIENCE}. ENGLAND: ROYAL SOC CHEMISTRY, 2024, roč.~12, č.~5, s.~1249-1262. ISSN~2047-4830. Dostupné z: https://doi.org/10.1039/d3bm01257c.

Přehled o publikaci