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

Jun Shao,Xudong Zhu,Bo Wei,Xiaoming Zheng,Zikai Cai,Longbao Feng,Rongpu Liang,Dongbing Ding,Tianyun Lan

doi:10.3389/fbioe.2020.575365

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. 1H 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 αvβ3 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.

Highlights

Gastric cancer (GC) is a common malignant tumor and ranks the second leading cause of cancerrelated death in the world, making it a serious threat to human health and quality of life
The preparation process of DSPE-PEG-RGD@indocyanine green (ICG) was shown in Scheme 1 and its molecular structure was further verified by 1H-NMR spectroscopy
Resonance peak at ∼7.0 ppm corresponded to δc (–CO–CH=) of the Mal group, which nearly disappeared in the spectrum of DSPE-PEG-RGD

Summary

Introduction

Gastric cancer (GC) is a common malignant tumor and ranks the second leading cause of cancerrelated death in the world, making it a serious threat to human health and quality of life. Accurate and early diagnosis of GC remains a significant clinical challenge. Endoscopic procedures such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), have been performed to treat GC in the early stage (Ban et al, 2018; Dahan et al, 2019). The diagnosis of the small tumor, the accurate resection of the tumor, etc. Those seriously affect the quality of life and survival of patients with GC

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Conclusion