智能型纳米化自体细胞膜载药系统的构建及其在胃癌靶向治疗中的评价

Improving tumor targeting and penentration of anticancer drugs is very important for tumor therapy. Based on our previous studies about drug delivery system which were supported by the National Natural Science Foundation of China, this program is aimed at the preparation of an intelligent nano-automembrane drug delivery system by the involvement of auto-erythrocyte membrane and a duai-targets and tumor penetrating fusion protein. So the ideal antitumor effects are under the premise that the drug could not only accumulate in the tumor, but also penetrate into the center of tumor. After nanoparticles loading paclitaxel, this study is focusing on the sustainable and high drug concentrations in tumors as well as the targeting effect, high penetration, pharmacokinetics, long circulation ability and safety of the system. We believe that our research will provide scientific evidence to develop new targeted drug carriers and transit them to clinical application.

提高抗肿瘤药物的肿瘤靶向性和穿透性是增强肿瘤治疗效果的关键问题。申请人所在的团队在前期国家自然科学基金资助纳米载药系统研究的基础上，采用生物安全度高、长循环的纳米化自体红细胞膜，以最新自主研制的具有双特异靶向性、高穿透性融合蛋白anti-EGFR-iRGD为依据，构建兼具肿瘤靶向特征和肿瘤高穿透性的纳米化自体细胞膜载药系统。通过实验条件及参数的优化，制备负载紫杉醇的智能型纳米化自体细胞膜载药微球，研究其靶向细胞毒作用、穿透能力、在体内的药代动力学、循环时间及安全性。研究该纳米载药体系对胃癌生长抑制作用，重点探讨该载药体系持续性提高肿瘤内药物浓度的效果，明确其作为一种新型的靶向药物控释体系在胃癌治疗中的价值，为临床应用提供科学依据。

提高抗肿瘤药物的肿瘤靶向性和穿透性是增强肿瘤治疗效果的关键问题。申请人所在的团队在前期国家自然科学基金资助纳米载药系统研究的基础上，采用生物安全度高、长循环的纳米化自体红细胞膜，将本课题组自主研制的具有双特异靶向性、高穿透性融合蛋白anti-EGFR-iRGD嵌插其中，构建了粒径大小均一、分散性好，载药量、包封率、稳定性达标的靶向纳米化自体细胞膜载紫杉醇系统。通过实验条件及参数的优化，制备负载紫杉醇的智能型纳米化自体细胞膜载药微球，研究其靶向细胞毒作用、穿透能力、在体内的药代动力学、循环时间及安全性。研究结果显示anti-EGFR-iRGD-RBCm-PTX在荷瘤裸鼠体内具有明显的肿瘤靶向性、肿瘤组织穿透性及抗肿瘤作用，相比其他对照组有明显的优势。研究结果认为anti-EGFR-iRGD-RBCm-PTX可以作为一种新型的靶向药物控释体系用于肿瘤的治疗。