Targeting effect of PEGylated liposomes modified with the Arg-Gly-Asp sequence on gastric cancer

Previous studies have demonstrated that the α5β1 integrin-mediated interaction with fibronectin (FN) occurs through the Arg-Gly-Asp (RGD) cell-binding sequence in repeat III10. Indocyanine green (ICG) is a near-infrared (NIR) optical dye that has been approved by the US Food and Drug Administration. In the present study, we developed an RGD-modified PEGylated liposome-encapsulated ICG (RGD-PLS-ICG) system mediated by integrin. RGD was conjugated covalently to the distal end of DSPE-PEG2000-NH2 lipid by amide binding. The characteristics and stability of the prepared liposomes were assessed. In vitro, SGC7901 cells with high expression of integrin α5β1 were selected by polymerase chain reaction (PCR) and western blotting. To confirm the targeting efficacies to gastric cancer, coumarin-6 was encapsulated as a fluorescent probe for in vitro study, and the targeting effect of RGD was detected by flow cytometry and confocal microscopy. In vivo, the bio distribution of RGD-PLS-ICG was studied by an in vivo imaging system in the tumor model. RGD-PLS-ICG and PLS-ICG had a higher UV absorbance spectrum and stability than free-ICG. Confocal microscopy and flow cytometry demonstrated that RGD-PLS-encapsulated coumarin-6 was efficiently associated with the SGC7901 cells, while limited interaction was found for the other groups. Moreover, the in vivo imaging of the liposomes indicated that RGD-PLS-ICG achieved more accumulation in the tumor tissues when compared with PLS-ICG. The significant in vitro and in vivo results suggest that RGD-PLS-ICG may be a promising fluorescent dye delivery system for targeting gastric cancer cell overexpression of integrin.