Study of the efficiency of cellular accumulation of doxorubicin supplied with a targeted delivery system based on phospholipid nanoparticles with integrin-directed peptide

   
Kostryukova L.V.1, Tereshkina Yu.A.1, Tikhonova E.G.1, Sanzhakov M.A.1, Bobrova D.V.1, Khudoklinova Yu.Yu.1

1. Institute of Biomedical Chemistry, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20226806437      PubMed Id: 36573410
Year: 2022  Volume: 68  Issue: 6  Pages: 437-443
Chemotherapeutic agents containing targeted systems are a promising pathway to increase the effectiveness of glioblastoma treatment. Specific proteins characterized by increased expression on the surface of tumor cells are considered as possible targets. Integrin αvβ3 is one of such proteins on the cell surface. It effectively binds the cyclic Arg-Gly-Asp (cRGD) peptide. In this study, the cRGD peptide-modified doxorubicin (Dox) phospholipid composition was investigated. The particle size of this composition was 43.76±2.09 nm, the ζ-potential was 4.33±0.54 mV. Dox was almost completely incorporated into the nanoparticles (99.7±0.58%). The drug release increased in an acidic medium (at pH 5.0 of about 35±3.2%). The total accumulation and internalization of Dox used the composition of phospholipid nanoparticles with the targeted vector was 1.4-fold higher as compared to the free form. In the HeLa cell line (not expressing αvβ3 integrin) this effect was not observed. These results suggest the prospects of using the cyclic RGD peptide in the delivery of Dox to glioblastoma cells and the feasibility of further investigation of the mechanism of action of the entire composition as a whole.
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Keywords: glioblastoma, phospholipid nanoparticles, cRGD, αvβ3 integrin, chemotherapy, doxorubicin
Citation:

Kostryukova, L. V., Tereshkina, Yu. A., Tikhonova, E. G., Sanzhakov, M. A., Bobrova, D. V., Khudoklinova, Yu. Yu. (2022). Study of the efficiency of cellular accumulation of doxorubicin supplied with a targeted delivery system based on phospholipid nanoparticles with integrin-directed peptide. Biomeditsinskaya Khimiya, 68(6), 437-443.
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