Folate receptor mediated targeted delivery of ricin entrapped into sterically stabilized liposomes to human epidermoid carcinoma (KB) cells: Effect of monensin intercalated into folate-tagged liposomes

Ricin was encapsulated into various sterically stabilized liposomes having different density of folate on the surface and the cytotoxicity of ricin in these liposomes was examined in KB cells. The effect of monensin in free and various sterically stabilized liposomal forms having different density of folate on the surface on the enhancement of cytotoxicity of ricin entrapped in these liposomes was also examined. It was observed that liposomal ricin having 0.5 mol% folate–PEG on the surface exhibits maximum cytotoxicity (IC50 = 1274 ng/ml) in KB cells as compared to non-targeted liposomes (IC50 = 3274 ng/ml). Monensin either in free form (266.2-fold) or liposomal form (291.5-fold) enhances the cytotoxicity of this targeted liposomal ricin significantly. This enhancement of the cytotoxicity of ricin entrapped in folate-targeted liposomes is further enhanced to 557.7-fold by monensin when it was delivered through folate-targeted (0.5 mol% folate–PEG) liposomes. The present study has clearly demonstrated that ricin entrapped in folate-tagged-sterically stabilized liposomes in combination with monensin intercalated in folate-tagged-sterically stabilized liposomes may have potential application for the treatment of cancer cells over-expressing folate receptors on the cell surface.

The effect of folate on the surface of liposomes on the cytotoxicity of ricin entrapped into liposomes in combination with monensin intercalated into folate tagged liposomes was examined in folate receptor positive human cancer cells. It was observed that ricin entrapped into liposomes having 0.5 mol% folate on the surface exhibit maximum cytotoxity. Monensin intercalated into folate-tagged liposomes significantly (557-7-fold) enhanced the cytotoxicity of liposomal ricin. The enhanced cytotoxicity of ricin entrapped in folate targeted liposomes is highly correlated with enhanced cellular association of these liposomes in KB cells as measured by double marker, entrapped aqueous marker (125I-ricin) and fluorescent surface marker (NBD-PC).Figure optionsDownload as PowerPoint slide