缺血性脑卒中治疗（IS）发病过程中脑组织“无血流”、“无复流”病理特性是IS脑内递药最大障碍。白细胞是唯一能够在IS缺血期、再灌期及恢复期全病程进入缺血脑组织的细胞，具胞吞和胞吐特性。本项目选择过氧化氢酶（Cat）为模型药，顺式乌头酸酐对其修饰增加电荷密度后将Cat载于PEG化聚左旋赖氨酸纳米粒（PEG-DGL-Cat-NP）；特异性交联剂增加PEG-DGL-Cat-NP紧密程度，提高Cat体内稳定性；然后将N-Ac-PGPGGC肽修饰于PEG-DGL-Cat-NP表面，使其通过与血循环中中性粒细胞、单核细胞及淋巴细胞发生高度结合并被内吞来构建纳米粒—白细胞联合载体，利用白细胞的趋化性携带活性药物在IS不同病程阶段进入缺血脑组织，然后通过白细胞与靶细胞之间相互作用递释药物进入靶细胞，实现IS全病程多级脑靶向递药，第一时间对抗白细胞造成的氧化损伤，创新性较强，有望真正解决IS治疗瓶颈。

Ischemic stroke (IS) is caused by a reduction in the blood supply to a part of the brain and subsequently receives returning blood containing leukocytes that may occlude small vessels and release toxic products. This course of ischemia/reperfusion makes it difficult for drugs to be delivered to the lesions. Leukocytes provide a unique opportunity for drug delivery to lesion and target cell. N-Ac-PGPGGC shows high affinity to monocytes, neutrophiles and lymphoctyes. Hence, N-Ac-PGPGGC can be used as a ligand to be modified on the surface of PEGlyated dendrigraft poly-lysines nanoparticles which loaded with catalase (PGP-PEG-DGL-Cat-NP). To enhance the stability of Cat, it was modified with cis-Aconitic anhydride to increase the negative-charge for better adsorption with PEG-DGL. Then, PGP-PEG-DGL-Cat-NP can enhance the stability of catalase and the affinity of nanoparticles with leukocytes to obtain a nanoparticle-cell combination carrier. It can delivery neuroprotection to the targeted-cell in the ischemic area using the chemotaxis of leukocytes during all the pathogenesis process. Thus, a multi-targeting drug delivery system (DDS) of leukocyte-nanoparticles combination to brain is to be obtained for IS therapy based on inflammation response.