荧光纳米粒子在小鼠胃癌皮下瘤模型近红外成像中的实验研究

目的 合成特异性靶向胃癌纳米粒子,借助自主搭建的近红外荧光腹腔镜,探讨该纳米粒子在胃癌精确诊断及完整切除中的价值。方法 将吲哚菁绿（ICG）通过自主装方式包覆于双亲性聚合物二硬脂酰基磷脂酰乙醇胺-聚乙二醇-马来酰亚胺（DSPE-PEG-Mal）,同时,用精氨酸-甘氨酸-天冬氨酸（RGD）多肽修饰,制备靶向纳米粒子DSPE-PEG-RGD@ICG。通过核磁谱图验证产物,吸收光谱检测光学性质。建立小鼠胃癌皮下瘤模型,在自主搭建的近红外荧光腹腔镜下检测及切除肿瘤。结果 核磁谱图验证产物与预期相符,并表现出与游离ICG相似的吸收光谱。在体内实验中,DSPE-PEG-RGD@ICG可特异性靶向胃癌,指导胃癌的完整切除。静脉给药4 h后,荧光腹腔镜可清楚显示肿瘤位置。小鼠胃癌皮下瘤检出率为91.8%,检出肿瘤的最小直径为4.9 mm。结论 成功制备了特异性靶向胃癌的纳米粒子DSPE-PEG-RGD@ICG,其光学特性与ICG相似,在近红外荧光腹腔镜引导下,可有效地协助外科医师对小鼠胃癌皮下瘤进行定位及完整切除。

Experimental study of near-infrared imaging of fluorescent nanoparticles in gastric cancer mouse models with subcutaneous tumors

Objective To synthesize a gastric cancer-specific nanoparticle and to explore the value of the nanoparticle in accurate diagnosis and complete resection of gastric cancer under the guidance of self-built near-infrared fluorescence laparoscopy. Methods Indocyanine green （ICG） was encapsulated into the amphiphilic polymer distearyl phosphatidylethanolamine-polyethylene glycol-Maleimide （DSPE-PEG-Mal） by self-assembly method. And the surface of the polymer was modified with arginine-glycine-aspartic acid polypeptide （RGD） to prepare targeted nanoparticles DSPE-PEG-RGD@ICG. The product was verified by NMR and the optical properties were detected by absorption spectrum. The gastric cancer mouse models with subcutaneous tumors were established, and the tumors were detected and resected under self-built near infrared fluorescence laparoscopy. Results The NMR spectra showed that the product was consistent with the expected product and showed a similar absorption spectra to free ICG. In in vivo experiment, DSPE-PEG-RGD@ICG could specifically target gastric cancer and guide the complete resection of tumors. At 4 h after intravenous administration, the location of tumors could be clearly displayed by fluorescence laparoscopy. The detection rate of subcutaneous tumors in gastric cancer mouse models was 91.8%, and the minimum diameter of detected tumors was 4.9 mm. Conclusions The successfully prepared nanoparticles targeting gastric cancer have optical properties similar to that of ICG, which can effectively assist surgeons in the complete resection of subcutaneous tumors in gastric cancer mice under the guidance of self-built fluorescence endoscopy system.