RESUMO
We studied the possibility of optimizing modular nanotransporters (MNTs) for the intracellular delivery of antibody fragments into the nuclei of cells of a specified type. Basic MNT with a reduced size retaining the desired functions was obtained, and the principal possibility of obtaining an MNT carrying an antibody fragment by microbiological synthesis was shown.
Assuntos
Portadores de Fármacos/química , Espaço Intracelular/metabolismo , Nanoestruturas/química , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/metabolismo , Linhagem Celular Tumoral , HumanosRESUMO
Modular nanotransporter (MNT) with C-terminal fragment of the p21 protein was synthesized and characterized, and its effect on DNA lesions was studied. This p21 fragment in MNT can significantly inhibit DNA repair in A431 human carcinoma cells after bleomycin treatment.
Assuntos
Bleomicina/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/química , Reparo do DNA/efeitos dos fármacos , Portadores de Fármacos/química , Nanoestruturas/química , Fragmentos de Peptídeos/química , Linhagem Celular Tumoral , HumanosRESUMO
The albumin-binding domain (ABD) with a site for its cleavage by tumor proteases was inserted in the structure of modular nanotransporters (MNTs), chimeric proteins for the delivery of anticancer drugs into the nuclei of cancer cells. The effectiveness of this cleavage was tested in both variants of created construct: "pure" ABD-MNT and the complex with albumin. The introduction of the ABD module into MNTs had no effect on the binding of MNT with receptors on the surface of the target cancer cells and on the preferential accumulation of MNTs in the nuclei of these cells. The use of thermophoresis allowed us to determine the equilibrium dissociation constants of the ABD-MNT complex with bovine and human serum albumins.
