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.
Ispol'zovanie khimiopreparatov, soderzhashchikh adresnye sistemy dostavki, predstavliaet soboĭ perspektivnoe napravlenie povysheniia éffektivnosti lecheniia glioblastomy. V kachestve misheneĭ rassmatrivaiutsia spetsificheskie belki, ékspressiia kotorykh na poverkhnosti opukholevykh kletok uvelichivaetsia. Takim belkom iavliaetsia integrin αvβ3, kotoryĭ éffektivno sviazyvaet tsiklicheskiĭ peptid Arg-Gli-Asp (cRGD). V dannoĭ rabote issledovana fosfolipidnaia kompozitsiia doksorubitsina (Dox), snabzhennaia cRGD peptidom. Razmer chastits kompozitsii sostavlial 43,76±2,09 nm, ζ-potentsial sootvetstvoval 4,33±0,54 mV. Dox prakticheski polnost'iu vstraivaetsia v nanochastitsy (99,7±0,58%). Pri izuchenii vysvobozhdeniia lekarstva v zavisimosti ot kislotnosti sredy bylo ustanovleno povyshennoe ego vysvobozhdenie v kisloĭ srede rN 5,0 (okolo 35±3,2%). Otsenka kletochnogo nakopleniia pokazala povyshenie obshchego nakopleniia i internalizatsii Dox v sostave fosfolipidnykh nanochastits s adresnym vektorom v ~1,4 raza po sravneniiu so svobodnoĭ formoĭ. Pri étom na linii kletok HeLa (ne ékspressiruiushchikh integrin αvβ3) podobnogo éffekta ne nabliudalos'. Poluchennye rezul'taty svidetel'stvuiut o perspektivnosti ispol'zovaniia tsiklicheskogo RGD peptida v dostavke Dox v kletki glioblastomy i tselesoobraznosti dal'neĭshego issledovaniia mekhanizma deĭstviia vseĭ kompozitsii v tselom.
Keywords: cRGD; chemotherapy; doxorubicin; glioblastoma; phospholipid nanoparticles.