Development of enzyme-loaded nano-sized polyion complex vesicles (PICsomes) for enzyme prodrug therapy

酶在体内的利用仍然是生物医学领域的一大挑战。酶的前体药物治疗是酶的一个很有前景的应用领域，而酶的纳米载体的开发是建立EPT金标准的一条有效线索。我们成功地制备了直径为100 nm的β-半乳糖苷酶负载PICsome，并保持了酶的活性。利用负载b-gal的PICsome作为酶载体，由于HMDER-bGAL通过囊泡壁的渗透，模型前药HMDER-bGAL被成功地转化为高荧光产物HMDER。在使用荷瘤小鼠的体内实验中，负载b-gal的PIC小体在肿瘤组织中积累，以产生HMDER。结果HMDER从PICsome释放并分布到整个肿瘤组织中并被细胞内化，然后进行肿瘤组织的可视化。

Utilization of enzymes in the body is still a big challenge in the biomedical field. One of promising applications of enzymes for therapeutic application is enzyme prodrug therapy, and development of nano-vehicles for enzymes is one effective clue to establish the golden standard of EPT. We succeed in the preparation of b-galactosidase loaded PICsome with the diameter of 100 nm, maintaining enzyme activity. Exploiting b-gal-loaded PICsomes as an enzyme vehicles, a model prodrug, HMDER-bGAL, was successfully converted into highly fluorescent product, HMDER, due to permeation of HMDER-bGAL through the vesicle wall. In in vivo experiments using tumor-bearing mice, b-gal-loaded PICsomes were accumulated in the tumor tissue, to produce HMDER. Resulted HMDER was released form PICsomes and distributed into the entire tumor tissues and internalized by cells, and then visualization of tumor tissues was performed.