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

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Publikace nespadá pod Fakultu sociálních studií, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.
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CHAROUSOVA Marketa KUDLIČKOVÁ PEŠKOVÁ Marie TAKACSOVA Paulina KAPOLKOVA Katerina HADDAD Yazan BILEK Jan SIVAK Ladislav BARTEJS Tomáš HEGER Zbynek PEKAŘÍK Vladimír

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj BIOMATERIALS SCIENCE
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www https://pubs.rsc.org/en/content/articlelanding/2024/bm/d3bm01257c
Doi http://dx.doi.org/10.1039/d3bm01257c
Klíčová slova DELIVERY-SYSTEM; NANOPARTICLES; APOFERRITIN; ENCAPSULATION; DOXORUBICIN; SOLUBILITY; NANOCAGE; SIRNA; NANOCLUSTERS; DEGRADATION
Popis 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.
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