Comprehensive Cancer Network and the European Society for Medical Oncology have recommended D2 radical surgery to improve the 5-year survival rate of gastric cancer patients

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. Introduction Gastric cancer is the fourth most common cancer and the second leading cause of death from malignant disease worldwide, with especially high mortality rates in East, South and Central Asia; in Central and Eastern Europe; and in South America (1). In D1 dissection, the stomach (total or distal) plus the perigastric lymph nodes are removed; and in D2 dissection, additional removal of the nodes along the left gastric area, common hepatic splenic zone and left hepatoduodenal artery is performed (2). The 3rd edition of ‘The Gastric Cancer Treatment Guidelines’ in Japan, defined D2 radical surgery as the standard operation. In recent years, D2 radical surgery has also been gradually accepted by European and American doctors. The United States National Comprehensive Cancer Network and the European Society for Medical Oncology have recommended D2 radical surgery to improve the 5-year survival rate of gastric cancer patients (3,4). However, follow-up study conducted over 15 years suggested that D2 operation is associated with lower locoregional recurrence and gastric-cancer-related death rates, yet had significantly higher postoperative mortality, morbidity and reoperation rates than D1 surgery (5). Obviously, a standardized operation may lead to an expansion in the scope of relative lymphadenectomy in some patients and increase unnecessary damage and risk. Therefore, the accurate resection of tumors, even accurate lymphadenectomy, is urgent and necessary. Integrin is a major family of cell surface receptors. It serves as the bridge for cell-cell and cell-extracellular matrix (ECM). Integrin α5β1, is one of the important members of the integrin family and is a major receptor of fibronectin (FN). Previous research has shown that integrin α5β1 identifies and combines with the Arg-Gly-Asp (RGD) sequence, an RGD sequence that is located in III10 of FN and is the site of cell attachment via α5β1 integrin on the cell surface (6-9). Integrin α5β1 plays an important role in tumor growth, invasion and metastasis (10-12). In recent years, research suggests that expression of integrin is associated with the differentiation and metastasis of gastric cancer (13), and integrin α5β1 may be an independent prognostic factor for gastric cancer patients (14). Therefore, artificial synthetic RGD, or an agent containing the RGD sequence has been used as a ligand to target gastric cancer (15,16). Indocyanine green (ICG) was approved by the FDA for use as a clinical near-infrared imaging agent, which has high safety, less adverse reactions, and a high signal-to-noise ratio Targeting effect of PEGylated liposomes modified with the Arg-Gly-Asp sequence on gastric cancer JIE DING, MIN FENG, FENG WANG, HAO WANG and WENxIAN GUAN Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China Received March 19, 2015; Accepted June 26, 2015 DOI: 10.3892/or.2015.4142 Correspondence to: Dr Wenxian Guan, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008,