Goto Akinori, Yen Hung-Chi, Anraku Yasutaka, Fukushima Shigeto, Lai Ping-Shan, Kato Masaru, Kishimura Akihiro, Kataoka Kazunori
Watarase Research Center, Kyorin Pharmaceutical CO., LTD., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
Department of Chemistry, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 402, Taiwan.
ACS Biomater Sci Eng. 2017 May 8;3(5):807-815. doi: 10.1021/acsbiomaterials.6b00562. Epub 2017 Apr 4.
Polyion complex vesicles (PICsomes) are polymeric hollow capsules composed of a unique semipermeable membrane, which may represent a versatile platform for constructing drug-loaded nanoformulation. However, it is difficult to retain water-soluble low-molecular-weight compounds (LMWCs) in the inner space of PICsome because of the high permeability of PIC membrane for LMWCs. Herein, we selected mesoporous silica nanoparticle (MSN) as a drug-retaining nanomatrix, and we demonstrated successful encapsulation of MSN into the PICsome to obtain MSN@PICsome. The efficacy of MSN loading, a ratio of the amount of MSN encapsulated in the PICsome to the amount of feed MSN, was at most 83%, and the diameter of resulting product was approximately 100 nm. The obtained MSN@PICsome was stably dispersed under the physiological condition, and showed considerable longevity in blood circulation of mice. Furthermore, the surface of MSN in MSN@PICsome can be modified without any deterioration of the vesicle structure, obtaining amino-functionalized and sulfonate-functionalized MSN@PICsomes (A-MSN@PICsome and S-MSN@PICsome, respectively). Both surface-modified MSN@PICsomes were successfully loaded with charged water-soluble low-molecular-weight compounds (LMWCs). Particularly, S-MSN@PICsome kept 8 wt % gemcitabine (GEM) per S-MSN, and released it in a sustained manner. GEM-loaded S-MSN@PICsome demonstrated marked cytotoxicity against cultured tumor cells, and achieved significant in vivo efficacy to suppress the growth of subcutaneously implanted lung tumor via intravenous administration.
聚离子复合囊泡（PIC囊泡）是由独特的半透膜组成的聚合物空心胶囊，它可能是构建载药纳米制剂的通用平台。然而，由于PIC囊泡膜对低分子量水溶性化合物（LMWCs）具有高渗透性，因此很难将其保留在PIC囊泡的内部空间中。在此，我们选择介孔二氧化硅纳米颗粒（MSN）作为药物保留纳米基质，并证明成功地将MSN封装到PIC囊泡中以获得MSN@PIC囊泡。MSN的负载效率（即封装在PIC囊泡中的MSN量与进料MSN量的比率）最高为83%，所得产物的直径约为100nm。所获得的MSN@PIC囊泡在生理条件下稳定分散，并在小鼠血液循环中显示出相当长的寿命。此外，MSN@PIC囊泡中MSN的表面可以被修饰而不会使囊泡结构有任何恶化，从而分别获得氨基官能化和磺酸盐官能化的MSN@PIC囊泡（分别为A-MSN@PIC囊泡和S-MSN@PIC囊泡）。两种表面修饰的MSN@PIC囊泡都成功地负载了带电荷的水溶性低分子量化合物（LMWCs）。特别地，S-MSN@PIC囊泡每个S-MSN保留8wt%的吉西他滨（GEM），并以持续的方式释放它。负载GEM的S-MSN@PIC囊泡对培养的肿瘤细胞表现出显著的细胞毒性，并通过静脉给药在体内实现了显著的抑制皮下植入肺肿瘤生长的效果。
