肿瘤归巢-穿膜肽介导靶向载药相变纳米粒用于肿瘤超声分子成像与治疗研究

项目名称： 肿瘤归巢-穿膜肽介导靶向载药相变纳米粒用于肿瘤超声分子成像与治疗研究

项目编号： No.81471675

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 任建丽

作者单位： 重庆医科大学

项目金额： 73万元

中文摘要： 基于申请者前期研究发现，自制靶向载基因及穿膜肽超声微泡造影剂能在一定程度上实现超声分子成像与靶向治疗，但由于血管内靶向缺陷-不能实现真正全细胞水平分子成像与靶向治疗，严重制约超声分子成像质量与靶向治疗水平的提高。因此，申请者设想研制一种新型的肿瘤归巢-穿膜肽介导同时具有细胞外积聚和细胞内渗透作用的靶向载药液-气相变型液态氟碳纳米粒即超声分子探针，利用肿瘤归巢-穿膜肽的肿瘤靶向及穿膜特性引导纳米粒深入靶向肿瘤细胞，并联合低强度聚焦超声使其相变成含气微泡、超声靶向破裂微泡技术（UTMD）介导肿瘤细胞靶向药物投递，实现高质量超声分子成像及安全高效的药物投递，以解决目前超声分子成像与靶向治疗中的核心问题。预期成功研制肿瘤归巢-穿膜肽介导的靶向载药液-气相变纳米粒，通过体内外实验定性定量评价该纳米粒的超声分子成像及靶向治疗效果，为超声分子成像诊断及UTMD介导药物递送治疗肿瘤提供一种新策略和新手段。

中文关键词： 肿瘤归巢-穿膜肽；靶向药物递送系统；相变；超声分子成像；肿瘤

英文摘要： Based on our previous research, we found that homemade targeted ultrasound microbubble contrast agent (UMCA) carring gene and cell-penetrating peptide can realize ultrasound molecular imaging and targeted therapy to some extent. However, because of intravascular targeted defect - UMCA can't achieve real level of whole cell molecular imaging and targeted therapy, it restricts severely ultrasound molecular imaging quality and the improvement of targeted therapy. Therefore, to solve the key problem of ultrasound molecular imaging and targeted therapy, this project will prepare a new targeted drug-loaded phase-shift nanoparticles mediated by tumor homing-penetrating peptide with the characteristic of extracellular accumulation and intracellular penetration (ultrasonic molecular probe). Nanoparticles penetrate tumor cells mediated by tumor targeting and penetrating property of tumor homing-penetrating peptide, combined with low intensity focused ultrasound (LIFU) to realize phase-shift and ultrasound-targeted microbubble destruction (UTMD) technology to realize targeted drug delivery in tumor cells, which achieve high quality ultrasound molecular imaging and efficient drug delivery. It is expected that targeted drug-loaded phase-shift nanoparticles mediated by tumor homing-penetrating peptide is prepared successfully, evaluated qualitatively and quantitatively the effect of ultrasound molecular imaging and targeted therapy in vivo and in vitro experiments, which provides a new strategy and method for ultrasound molecular imaging diagnosis and tumor treatment mediated by UTMD drug delivery system.

英文关键词： Tumor homing-penetrating peptide;Targeted drug delivery system;Phase-shift;Ultrasound molecular imaging;Tumor