基于血管靶向栓塞策略的抗肿瘤纳米药物设计和机制研究

项目名称： 基于血管靶向栓塞策略的抗肿瘤纳米药物设计和机制研究

项目编号： No.31200752

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 李素萍

作者单位： 国家纳米科学中心

项目金额： 23万元

中文摘要： 选择性栓塞肿瘤组织血管从而诱发肿瘤组织的缺血性坏死是一种很有前景的抗肿瘤策略。本研究将采用纳米技术，结合促凝药物/试剂的生物学特性，设计并构建生物相容性、可靶向作用于肿瘤组织血管的纳米促凝药物新剂型，实现纳米颗粒富集导致物理性栓塞和促凝药物释放诱发生物性栓塞的协同效应，从而阻断肿瘤血供，引发肿瘤缺血性坏死，发挥抗肿瘤作用。本研究将通过凝血功能测定、小动物活体成像、免疫组化等技术手段评价纳米促凝药物的生物安全性并研究其体内代谢行为；在荷瘤小鼠模型上评价纳米药物的抗肿瘤效果，并通过细胞功能分析揭示其在肿瘤血管中促凝的作用机制和细胞毒性。本研究的开展将为开辟肿瘤血管靶向、纳米材料、促凝药物三者有机结合的血管靶向治疗新途径奠定一定的基础，有望为肿瘤血管靶向治疗提供一种高效的药物新剂型。

中文关键词： 肿瘤血管；凝血酶；纳米颗粒；肿瘤靶向肽；肿瘤梗塞

英文摘要： Selective thrombotic formation in tumor vessels to induce subsequent tumor necrosis is a promising anti-tumor strategy. Nanoparticles can be engineered to perform multiple functions, which provides significant advantages over simple drug entities. In this study, we designed a biocompatible nanoparticle-delivery system to selectively trigger blood clot formation in tumor vasculature. The nanoparticles would be loaded with coagulant drugs and specially engineered to link tumor homing peptide on their surface. The interaction of the nanoparticles and tumor vasculature would induce thrombotic formation in tumor blood vessels by the synergetic effects of nanoparticle accumulation and drug release from the nanoparticles. Tumor specific thrombosis will occlude tumor vasculature and cut off nutrition and oxygen supplies of tumor, and consequenetly exert anti-tumor effects. The safety and in vivo behavior of nanoparticles will be analyzed by clotting assay, in vivo imaging, H&E staining and immune histological analyses. The anti-tumor effects will be assessed using both tumor xenografts and tumor cells. The mechanism of anti-tumor effects of nanoparticles will be further investigated by cell viability assay. This study will lay the foundation for further developing novel nanotechnology-enabled cancer therapeutic agents

英文关键词： Tumor blood vessels；Thrombin；Nanoparticle；Tumor targeted peptide；Tumor infarction