多功能明胶酶靶向纳米粒子对进展期胃癌转移性淋巴结的示踪作用研究

The accurate gastric cancer surgery requiring the precise evaluation of lymph node metastasis. Recently, the approach to evaluate lymph node metastasis effectively has not been found. Nano-composite material, designed for tumor imaging and tracing, provided us a novel approach to evaluate lymph node metastasis in the patients with gastric cancer. However, The effect of these nano-composite material relies on the backflow of lymph system. Unfortunately, lymph vessels were often obstructed by tumor cells in advanced gastric cancer, and this may restrain the application of these nanoparticles. Based on previous studies, we developed the gelatinase-targeted nanoparticle consisting of a gelatinase-cleavage peptide with poly(ethylene glycol) (PEG) and poly(ε-caprolactone)(PCL)-based structure. After administration intravenous into tumor-beared animals, this nanoparticle accumulated in tumor tissue with tumor-targeted feature. These gave a rise to a hypothesis that states that the multifunctional nanoparticle packed with USPIO, indocyanine green and gelatinase may provide a potential approach to evaluate lymph node metastasis precisely in gastric cancer. We will investigated this issues based on molecule, vitro and vivo studies. This study will provide a novel nanomaterial for evaluating lymph node metastasis in gastric cancer, and also provide an approach to the accurate surgery for gastric cancer therapy.

精确清扫淋巴结，可使胃癌患者避免承受不必要的创伤和风险，同时也不会因淋巴结清扫范围不足影响手术疗效，但至今尚缺乏精确的评估手段。纳米材料应用于胃癌转移淋巴结的评估是一个新兴领域，是有望实现转移淋巴结精确评估的潜在手段。但目前与胃癌转移淋巴结示踪相关的非靶向纳米材料，借助于ERP效应可以在淋巴结有一定聚集，但其信号微弱，难以精确定位胃癌转移淋巴结。我们前期研究发现，将明胶酶底物肽段插入两嵌段高分子纳米载体单甲氧基聚乙二醇-聚己内酯中，构建的明胶酶靶向纳米粒子，经静脉注射入后，可在荷瘤动物模型的肿瘤组织内高积聚，具有良好的肿瘤靶向效应。在此基础上，我们拟将USPIO与吲哚菁绿同时包裹在该纳米载体上，使其兼具磁共振显影和术中示踪的功能。我们将从分子-细胞-体内三个层面研究新型纳米粒子的示踪效果及分布代谢特点，为胃癌转移淋巴结术前及术中示踪提供一种新的纳米材料，为胃癌精确清扫淋巴结提供技术支撑。

纳米材料应用于胃癌术中淋巴结转移评估属新兴领域，具备重大的临床意义与良好的应用前景。本课题组在前期已构建的明胶酶靶向纳米粒子基础上，在本项目中将USPIO与ICG包裹在该纳米载体上，从分子、细胞、体内三个层面探讨了该新型纳米粒子体内胃癌转移淋巴结的靶向效果。本项目构建了稳定、均一的明胶酶靶向多功能高分子纳米粒子，发现其在体内胃癌转移淋巴结中具有靶向积聚能力，证实其能够为术前MR显影与术中示踪胃癌转移淋巴结提供有力帮助。本项目的研究成果为实现术前、术中准确判断胃癌淋巴结转移、个体化精确手术治疗胃癌提供了一定的数据支撑，为研发新型明胶酶靶向多功能高分子纳米粒子及其临床转化应用提供了一定科学依据。