具有酸敏载药内核的仿生纳米红细胞

Based on the previous studies, starting from cancer treatment, the project will combine the outstanding performance of polymer nanocarriers with natural erythrocytes, and construct red cell membrane coated acid-sensitive drug-loading nanoparticle system. By targeting ligand - phospholipid's modification to the surface of red cell membrane, the active targeting for cancer cells will be addressed;The compositionand physical structure of polymer nanocarriers will be adjusted to realize the rapid release of the drug, entering the lysosome in the tumor tissue and cell with weak acid environment. The nanosystem in the preject can not only simulate the characteristics of the body transport of red blood cells, but also greatly improve drug bioavailability, and significantly reduce toxicity caused by drug leaky. Therefore, it is expected to overcome some formidable obstacles in drug chemotherapy, and exhibit get better effect of cancer therapy.

在前期研究基础上，从肿瘤治疗出发，本项目将性能优异的聚合物纳米载体与红细胞载体结合起来，构建具有酸敏载药内核的仿生纳米红细胞系统。通过将靶向配体-磷脂分子修饰到仿生纳米红细胞膜表面，实现对癌细胞的主动靶向传输；同时对聚合物纳米载体的基质成分和物理结构的调节，可以进入机体后在肿瘤组织和细胞内溶酶体弱酸环境下实现药物的快速释放。从而模拟红细胞体内输运的特性，极大地提升药物的生物利用度，还可以显著降低因药物施用造成的系统毒性，有望克服药物化疗中一些难以逾越的障碍，获得更好的肿瘤治疗效果。

近几十年来，工程纳米治疗剂的开发和应用在癌症治疗等方面取得了显著进展。随着对肿瘤微环境和材料科学的深入了解，能够响应各种内、外部刺激源，按需释放有效载荷的智能响应型纳米药物载体成为新一代纳米药物运输体系的新工程策略。基于智能纳米药物体系的优异性，本项目围绕完善功能化纳米载体设计，提高肿瘤治疗效果以及减少毒副作用这一目标，选择了具有良好生物相容性的生物大分子牛血清白蛋白、红细胞膜以及天然葡萄糖氧化酶（GOx）为纳米载体，设计了具有pH和谷胱甘肽（GSH）双重响应、光触发释放以及酶催化响应的四种纳米药物递送系统，用于化疗药物、光敏试剂或siRNA在肿瘤部位的定点和响应性释放，实现了肿瘤靶向、实时跟踪、多功能治疗等作用。