Development of magnetic anionic liposome/atelocollagen complexes for efficient magnetic drug targeting.
Development of magnetic anionic liposome/atelocollagen complexes for efficient magnetic drug targeting.
复制标题
开发磁性阴离子脂质体/去端肽胶原复合物，用于有效的磁性药物靶向。
DOI：
10.1080/10717544.2017.1402219
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发表时间：
2017-11
期刊：
影响因子：
6
通讯作者：
Fujita T
中科院分区：
文献类型：
--
作者：
Kono Y;Nakai T;Taguchi H;Fujita T
磁性纳米颗粒脂质体(磁性脂质体)被认为是一种很有前途的定点给药载体。在表面电荷方面，磁性阴离子脂质体(MAG-AL)比磁性阳离子脂质体(MAG-CL)毒性小，但细胞结合和摄取效率低。在本研究中，我们构建了MAG-AL与胶原蛋白(ATCOL)的复合物，ATCOL是一种生物相容性和最低免疫原性的生物材料，以改善MAG-AL的细胞摄取性能。当MAG-AL与ATCOL络合时，MAG-AL在磁场下对小鼠巨噬细胞样细胞系RAW264细胞的结合和/或摄取显著增加，其中以5 µg/mLATCOL构建的络合物的细胞结合率最高。该复合体在磁场作用下表现出脂质体浓度依赖性和时间依赖性的细胞结合，其细胞摄取效率与MAG-CL相当。此外，MAG-CL具有明显的细胞毒作用，且呈脂质体浓度依赖关系，而MAG-AL/ATCOL复合体对RAW264细胞无细胞毒作用。此外，即使在血清存在的情况下，MAG-AL/ATCOL复合体也能在RAW264细胞中有效地结合，并且在大鼠静脉注射磁场后，它们在磁场暴露区域的肝脏聚集显著增加。这些结果表明，MAG-AL/ATCOL络合物可能是一种安全有效的磁性药物载体。
Magnetic nanoparticle-incorporated liposomes (magnetic liposomes) are considered a promising site-specific drug delivery carrier vehicle. With regard to their surface charge, magnetic anionic liposomes (Mag-AL) demonstrate little toxicity in comparison with magnetic cationic liposomes (Mag-CL), whereas their cellular association and uptake efficiency are low. In the current study, we constructed complexes of Mag-AL and atelocollagen (ATCOL), which is a biocompatible and minimally immunogenic biomaterial, to improve the cellular uptake properties of Mag-AL in vitro and in vivo. The cellular association and/or uptake of Mag-AL in RAW264 cells, a murine macrophage-like cell line, under a magnetic field was significantly increased when Mag-AL was complexed with ATCOL, and the highest cellular association was observed with complexes constructed using 5 µg/mL of ATCOL. The complexes showed liposome concentration-dependent and time-dependent cellular association under a magnetic field, and their cellular uptake efficiency was comparable with that of Mag-CL. In addition, Mag-CL showed significant cytotoxicity in a liposome concentration-dependent manner, whereas Mag-AL/ATCOL complexes produced no cytotoxic effect against RAW264 cells. Furthermore, the efficient cellular association of Mag-AL/ATCOL complexes in RAW264 cells was observed even in the presence of serum, and their liver accumulation was significantly increased at a magnetic field-exposed region after intravenous injection in rats. These results indicate that Mag-AL/ATCOL complexes could be a safe and efficient magnetic responsive drug carrier.
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