Size-tuning of self-assembled hollow particles Nano-PICsomes and application to protein delivery system

我们开发了一种新型的多离子络合物(PIC)纳米结构，它是由一系列相反电荷的水溶性聚合物在水介质中简单混合而成的，主要是由生物相容的聚乙二醇和多氨基酸S组成的嵌段共聚物。因此，我们建立了单分散的中空粒子--纳米PICome的制备方法，其特征是囊泡直径在100-400 nm之间可方便地调节。对不同大小的纳米颗粒在荷瘤小鼠体内的详细生物分布进行了研究。药代动力学分析表明，直径为150~200 nm的PICome明显延长了血液循环。以长循环纳米颗粒为标尺，确定了区分正常组织和肿瘤组织渗透性的临界纳米载体大小(~150 nm)。

We have developed novel polyion complex (PIC) nano-architectures prepared by the simple mixing of a set of oppositely charged water-soluble polymers, mainly, block copolymers consisting of biocompatible poly(ethylene glycol) (PEG) and poly(amino acid)s in an aqueous medium. As a result, we established the preparation method of monodispersed hollow particles, Nano-PICsomes, which are characterized by facile tuning of vesicle size over 100-400 nm in diameter. Detailed biodistribution of the various sizes of Nano-PICsomes was examined in tumor-bearing mice. From pharmacokinetic analyses, PICsomes with the diameter of 150-200 nm showed much prolonged blood circulation. Critical size of nanocarriers (～150 nm) discriminating the permeability into normal and tumor tissues was determined by the use of long-circulating Nano-PICsome as a ruler.