Targeting Fluorescence Imaging of RGD-Modified Indocyanine Green Micelles on Gastric Cancer

Abstract

Early diagnosis and complete resection of the tumor is an important way to improve the quality of life of patients with gastric cancer. In recent years, near-infrared (NIR) materials show great potential in fluorescence-based imaging of the tumors. To realize a satisfying intraoperative fluorescence tumor imaging, there are two pre-requirements. One is to obtain a stable agent with a relatively longer circulation time. The second is to make it good biocompatible and specific targeting to the tumor. Here, we developed an RGD-modified Distearyl acylphosphatidyl ethanolamine-polyethylene glycol micelle (DSPE-PEG-RGD) to encapsulate indocyanine green (ICG) for targeting fluorescence imaging of gastric cancer, aimed at realizing tumor-targeted accumulation and NIR imaging. 1 H NMR spectroscopy confirmed its molecular structure. The characteristics and stability results indicated that the DSPE-PEG-RGD@ICG had a relatively uniform size of <200 nm and longer-term fluorescence stability. RGD peptides had a high affinity to integrin α v β 3 and the specific targeting effect on SGC7901 was assessed by confocal microscopy in vitro. Additionally, the results of cytotoxicity and blood compatibility in vitro were consistent with the acute toxicity test in vivo, which revealed good biocompatibility. The biodistribution and tumor targeting image of DSPE-PEG-RGD@ICG were observed by an imaging system in tumor-bearing mice. DSPE-PEG-RGD@ICG demonstrated an improved accumulation in tumors and longer circulation time when compared with free ICG or DSPE-PEG@ICG. In all, DSPE-PEG-RGD@ICG demonstrated ideal properties for tumor target imaging, thus, providing a promising way for the detection and accurate resection of gastric cancer.

Safety and efficacy of indocyanine green near-infrared fluorescent imaging-guided lymph nodes dissection during radical gastrectomy for gastric cancer: A systematic review and meta-analysis

“…Shao et al. ( 50 ) developed an RGD-modified distearyl acylphosphatidyl ethanolamine-polyethylene glycol micelle (DSPE-PEG-RGD) to encapsulate indocyanine green (ICG) and found that it had an improved accumulation in tumors and a longer circulation time. It is believed that better tracers will emerge in the future to guide the implementation of more precise radical gastrectomy.…”

Analysis of safety and efficacy of laparoscopic radical gastrectomy combined with or without indocyanine green tracer fluorescence technique in treatment of gastric cancer: a retrospective cohort study

“…The tripeptide sequence [arginine-glycine-aspartate [(RGD)] ligand can specifically bind with αvβ3 integrin, which can be specifically expressed in malignant gastric tumor cells (34). Modified by RGD and encapsulating ICG, micelle has a specific targeting effect and significant biocompatibility for gastric tumor-bearing mice, which provides a further research strategy for complete resection of gastric cancer (35). In their study, Shao et al provided a biocompatible theranostic nanoparticle with enhanced tumor-targeting ability for accurate near-infrared imaging in gastric cancer (36).…”

Opportunities and Challenges of Nanoparticles in Digestive Tumours as Anti-Angiogenic Therapies

“…In addition, new technologies such as near-infrared (NIR) fluorescence imaging can be used to observe the tissue morphology and metabolism, providing additional possibilities to detect important anatomical structures and tumour lymph node metastasis in real-time during surgery ( 86 ). The wavelength of NIR fluorescence is from 700 to 900 nm, with high tissue penetration (at the centimetre level) ( 87 ). After packaging NIR agents into nanoparticles and injection, the fluorescence signal can be captured by a laparoscopic fluorescent imaging system in real time, while human eyes are not sensitive to the NIR wavelength, and their presence will not change the surgical field.…”