Asialoglycoprotein receptors are highly abundant on the hepatocyte surface and have specific binding sites for blood serum glycoproteins. Such discovery resulted in development of liver-targeted drug delivery systems because modification of the liposomal surface by carbohydrate derivatives results in an increase of endocytosis, which facilitates selective uptake of such systems by hepatocytes. In this study we have synthesized novel lactose derivatives containing a palmitic hydrophobic domain. They were used for modification of the liposome surface. Transfection activity of modified liposomes was analyzed on the HepG2 cell line (hepatocytes) and showed an increase in the transfection efficiency as compared to the non-modified liposomes. At the same time transfection activities of modified and non-modified liposomes were similar in the case of a non-hepatocyte cell line (293T). The novel lactose-based glycoconjugates may be a promising tool for developing efficient vectors for delivery of nucleic acids to hepatocytes.
Asialoglikoproteinovye retseptory iavliaiutsia naibolee rasprostranennym tipom retseptorov na poverkhnosti kletok pecheni i obladaiut spetsifichnymi uchastkami sviazyvaniia dlia glikoproteinov syvorotki krovi. Éto sposobstvuet sozdaniiu adresnykh liposomal'nykh sistem dostavki lekarstv, sposobnykh selektivno dostavliat' soderzhimoe v kletki pecheni. Modifikatsiia liposomal'noĭ poverkhnosti proizvodnymi uglevodov privodit k uvelicheniiu éndotsitoza, chto sposobstvuet selektivnomu pogloshcheniiu takikh sistem gepatotsitami. V dannoĭ rabote byli sintezirovany neoglikokon"iugaty na osnove laktozy s ostatkom pal'mitinovoĭ kisloty v gidrofobnom domene. Uglevodsoderzhashchie amfifily ispol'zovali dlia modifikatsii liposomal'noĭ poverkhnosti. Issledovaniia transfektsionnoĭ aktivnosti vodnykh dispersiĭ, provedenye na spetsificheskoĭ linii kletok HepG2 (gepatotsity), pokazali povyshenie éffektivnosti po sravneniiu s nemodifitsirovannymi liposomami, v to vremia kak aktivnost' modifitsirovannykh i nemodifitsirovannykh liposom v otnoshenii nespetsifichnoĭ linii kletok 293T byla odinakovoĭ. Éto svidetel'stvuet o potentsial'noĭ vozmozhnosti ispol'zovaniia novykh neoglikokon"iugatov dlia dostavki nukleinovykh kislot adresno v kletki pecheni.
Keywords: glycoconjugates; hepatocytes; liposome modification; targeted transport.