Neutralization Of Lenvatinib Charge Hampers Encapsulation Into Ferritin Nanocages

Lenvatinib is an oral multi-target tyrosine-kinase (TK) inhibitor. Ferritins are proteins naturally occurring in human body, where they are responsible for the iron storage, transport and harmful ferrous species detoxification. The ferric-ions-free apo-form of ferritins can be used for drug encapsulation and delivery to tumor cells. To avoid harmful side effects and increase the anticancer efficiency, we investigated to prepare lenvatinib-loaded apoferritin (ApoLen) nanoparticles. We tested various experimental conditions, i.e. different lenvatinib solvents and pH. Nevertheless, the construction of ApoLen nanoparticles was not successful. Therefore, lenvatinib interactions with the apoferritin cavity as well as lenvatinib encapsulation into the ApoLen nanoparticles were studied in silico using molecular dynamics (MD) simulations. In accordance with experimental results, theoretical models demonstrated that lenvatinib molecules are not suitable for preparation of ApoLen nanoparticles.