Bladder uptake of liposomes after intravesical administration occurs by endocytosis.
Bladder uptake of liposomes after intravesical administration occurs by endocytosis.
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DOI：
10.1371/journal.pone.0122766
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tyagi P
中科院分区：
文献类型：
--
作者：
Rajaganapathy BR;Chancellor MB;Nirmal J;Dang L;Tyagi P
脂质体已用于治疗和作为膀胱中的局部药物递送系统。然而，膀胱细胞摄取脂质体的确切机制尚不清楚。在本研究中，我们研究了内吞作用的脂质体的摄取培养的人UROtsa细胞的尿路上皮和大鼠膀胱。将UROtsa细胞在含有胶体金颗粒的脂质体的无血清培养基中在37°C或4°C下孵育2小时。在37°C下孵育的细胞的透射电子显微镜（TEM）图像发现细胞内含有金的内吞囊泡。相比之下，在4°C下与脂质体孵育的细胞中仅观察到细胞外结合。在4°C下不存在脂质体内化表明需要能量依赖性内吞作用作为脂质体进入尿道的主要机制。流式细胞术分析显示，脂质体在37°C下的摄取经由网格蛋白介导的内吞作用发生。基于这些观察，我们提出网格蛋白介导的内吞作用是脂质体进入膀胱尿路上皮层的主要途径，并且这里的发现支持脂质体在膀胱内药物递送中的有用性。
Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM) images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery.
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