Preventing the cytotoxic effects of tyrosine kinase inhibitors on healthy breast cells through loading into the ferritin nanocages

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F20%3A43918634" target="_blank" >RIV/62156489:43210/20:43918634 - isvavai.cz</a>

Alternative codes found

RIV/00216305:26620/20:PU137947

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Preventing the cytotoxic effects of tyrosine kinase inhibitors on healthy breast cells through loading into the ferritin nanocages

Original language description

This study is focused on the antiproliferative effects of tyrosine kinase inhibitors (TKIs) loaded into the protein cage ferritin. Since many TKIs show high cytotoxicity not only towards their target, cancer cells, but also towards healthy surrounding tissue, the prevention of these adverse effects is of utmost importance. Development of nanocarriers with loaded active agents has been proven to help minimize this off-target cytotoxicity. It is also very suitable for poorly water soluble pharmaceuticals. In this study, we focused on targeting TKIs, insoluble agents, which target vascular endothelial growth factor. Preserved cytotoxic effect of chemotherapeutics after their loading to nanocarriers is one of the crucial point of the loading process. During nanoconstruct synthesis, effective loading of TKIs (lenvatinib, vandetanib) to the protein nanocage ferritin was essential. The aim was to prevent cytotoxicity towards healthy cells; neverthe-less, loss of cytotoxicity towards cancer cells had to be prevented. Therefore, after successful loading process of TKIs to the ferritin it was necessary to verify maintain-ing the level of their cytotoxicity towards the breast cancer cell lines T-47D (PR+, ER+, HER2-, FR+, MCF-7 (PR+, ER+, HER2-, FR-), as well as healthy breast cell line HBL-100 and blood elements. For this purpose, in vitro tests of cytotoxicity were performed, quantifying the antiproliferative effect as well as level of apoptosis after treatment of cell lines. For evaluation of nanocon-struct internalization and their colocalization inside the cell, confocal laser scanning microscopy was used. Antiproliferative effect of nanoconstructs were tested via clonogenic assay and inhibition of cell migration via wound healing assay. The synthesized targeted ferritin nanoconstructs were able to prevent the cytotoxicity of TKIs to healthy cells while maintaining the cytotoxicity to cancer cells.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA18-10251S" target="_blank" >GA18-10251S: Comprehensive insight into mechanisms of action and metabolism of tyrosine kinase inhibitors and a study of ways increasing their antitumor efficiency</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů