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。酶的治疗应用前景之一是酶前药物治疗，而酶的纳米载体的开发是建立EPT金标准的有效线索之一。我们成功地制备了直径为100 nm的装载b-半乳糖苷酶的PICsome，并保持了酶的活性。利用装载b-gal的PICsomes作为酶载体，模型前药hder - bgal通过囊泡壁渗透，成功转化为高荧光产物HMDER。在荷瘤小鼠体内实验中，载b-gal的picsome在肿瘤组织中积累，产生HMDER。结果HMDER从PICsomes释放到整个肿瘤组织并被细胞内化，实现肿瘤组织可视化。

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.