Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System

Škubalová, Zuzana; Rex, Simona; Sukupova, Martina; Zahalka, Martin; Skládal, Petr; Přibyl, Jan; Michalkova, Hana; Weerasekera, Akila; Adam, Vojtěch; Heger, Zbyněk

doi:10.2147/ijn.s275808

Cited by 7 publications

(6 citation statements)

References 60 publications

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“…[ 16 ] managed to encapsulate platinum anticancer drugs into apoferritin after pH-mediating disassembly/reassembly that cisplatin or carboplatin were loaded in apoferritin. Other small molecules drugs, including paclitaxel [ 19 – 21 ], streptomycin [ 51 ], quercetin [ 22 ], curcumin [ 22 , 23 ], saponin [ 15 ], epirubicin [ 24 ], carbachol [ 42 ], atropine [ 42 ], mitoxantrone [ 25 ], kartogenin [ 26 ], ZnF 16 Pc [ 27 ], idarubicin [ 29 ], vandetanib [ 30 ], lenvatinib [ 30 ], vandetanib [ 31 ] and camptothecin [ 32 ] were also encapsulated in ferritin nanocage by this loading method.…”

Section: Loading Methods For Ferritin-based Nanomedicinementioning

confidence: 99%

“…Hydrophobic gefitinib was encapsulated in ferritin by incubation at 4 °C with a quite high encapsulation efficiency of 55%. Other hydrophobic drugs such as β-lapachone [ 34 ], vandetanib [ 30 ] and lenvatinib [ 30 ] were also reported to be loaded in ferritin by diffusion. In addition, another potential pathway at two-fold axis identified by Jiang et al.…”

Section: Loading Methods For Ferritin-based Nanomedicinementioning

confidence: 99%

“…Kubalova et al. [ 30 ] compared diffusion with pH-induced loading method in encapsulating tyrosine kinase inhibitors (TKIs) vandetanib and lenvatinib. Both methods showed similar loading efficiency, however TKIs loaded by diffusion exerted markedly higher anticancer activity than loaded by pH-induced disassembly/reassembly, indicating that the harsh acidic condition during pH-induced encapsulation was detrimental to the TKIs’ structure and activity.…”

Section: Loading Methods For Ferritin-based Nanomedicinementioning

confidence: 99%

“…Ferritin, with advantages including excellent histocompatibility, low immunogenicity, size uniformity, intrinsic tumor targeting, rich functional modification sites and BBB-crossing ability, has been widely studied for delivery of small molecule anti-tumor drugs ( Table 3 ). It can improve the solubility and druggability of insoluble drugs, such as paclitaxel [ 19 , 119 , 120 ], cisplatin [ 16 , 88 , 17 ], curcumin [ 22 , 23 ], gefitinib [ 35 ], vandetanib [ 30 ] and lenvatinib [ 30 ].…”

Section: Application Of Ferritin-based Nanomedicinementioning

confidence: 99%

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Ferritin-based nanomedicine for disease treatment

Zhu

Cao

et al. 2023

Medical Review

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Ferritin is an endogenous protein which is self-assembled by 24 subunits into a highly uniform nanocage structure. Due to the drug-encapsulating ability in the hollow inner cavity and abundant modification sites on the outer surface, ferritin nanocage has been demonstrated great potential to become a multi-functional nanomedicine platform. Its good biocompatibility, low toxicity and immunogenicity, intrinsic tumor-targeting ability, high stability, low cost and massive production, together make ferritin nanocage stand out from other nanocarriers. In this review, we summarized ferritin-based nanomedicine in field of disease diagnosis, treatment and prevention. The different types of drugs to be loaded in ferritin, as well as drug-loading methods were classified. The strategies for site-specific and non-specific functional modification of ferritin were investigated, then the application of ferritin for disease imaging, drug delivery and vaccine development were discussed. Finally, the challenges restricting the clinical translation of ferritin-based nanomedicines were analyzed.

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Section: Loading Methods For Ferritin-based Nanomedicinementioning

confidence: 99%

Section: Loading Methods For Ferritin-based Nanomedicinementioning

confidence: 99%

Section: Loading Methods For Ferritin-based Nanomedicinementioning

confidence: 99%

Section: Application Of Ferritin-based Nanomedicinementioning

confidence: 99%

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Ferritin-based nanomedicine for disease treatment

Zhu

Cao

et al. 2023

Medical Review

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“…23 Among them, various types of ferritins have been employed to enhance the bioavailability of poorly soluble compounds such as wogonin, vandetanib, lenvatinib, and others. 24,25 Therefore, in the present study, we employed recombinant HsaFtH to prepare a first Diph protein-based nanoformulation and subsequently test its biological properties with a special emphasis on antiviral activity against ZIKV, WNV, TBEV and SARS-CoV-2.…”

Section: Formulation and Characterization Of Diph@hsafth Nanoparticlesmentioning

confidence: 99%

Nanoformulation of the Broad-Spectrum Hydrophobic Antiviral Vacuolar ATPase Inhibitor Diphyllin in Human Recombinant H-ferritin

Vojnikova,

Sukupova,

Stefanik

et al. 2024

IJN

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Background: As highlighted by recent pandemic outbreaks, antiviral drugs are crucial resources in the global battle against viral diseases. Unfortunately, most antiviral drugs are characterized by a plethora of side effects and low efficiency/poor bioavailability owing to their insolubility. This also applies to the arylnaphthalide lignin family member, diphyllin (Diph). Diph acts as a vacuolar ATPase inhibitor and has been previously identified as a promising candidate with broad-spectrum antiviral activity. However, its physicochemical properties preclude its efficient administration in vivo, complicating preclinical testing. Methods: We produced human recombinant H-ferritin (HsaFtH) and used it as a delivery vehicle for Diph encapsulation through pHmediated reversible reassembly of HsaFtH. Diph nanoformulation was subsequently thoroughly characterized and tested for its nontarget cytotoxicity and antiviral efficiency using a panel of pathogenic viral strain. Results: We revealed that loading into HsaFtH decreased the undesired cytotoxicity of Diph in mammalian host cells. We also confirmed that encapsulated Diph exhibited slightly lower antiviral activity than free Diph, which may be due to the differential uptake mechanism and kinetics of free Diph and Diph@HsaFtH. Furthermore, we confirmed that the antiviral effect was mediated solely by Diph with no contribution from HsaFtH. Conclusion: It was confirmed that HsaFtH is a suitable vehicle that allows easy loading of Diph and production of highly homogeneous nanoparticles dispersion with promising broad-spectrum antiviral activity.

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