Anti-alpha8 integrin immunoliposomes in glomeruli of lupus-susceptible mice: a novel system for delivery of therapeutic agents to the renal glomerulus in systemic lupus erythematosus.
Anti-alpha8 integrin immunoliposomes in glomeruli of lupus-susceptible mice: a novel system for delivery of therapeutic agents to the renal glomerulus in systemic lupus erythematosus.
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DOI：
10.1002/art.24026
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发表时间：
2008-12
影响因子：
--
通讯作者：
Bagavant, Harini
中科院分区：
文献类型：
--
作者：
Scindia, Yogesh;Deshmukh, Umesh;Thimmalapura, Pushpa-Rekha;Bagavant, Harini
肾小球系膜细胞是狼疮性肾小球肾炎（GN）发病机制的积极参与者。因此，将治疗剂靶向递送至系膜细胞将是一种有吸引力的治疗方法。然而，缺乏独特的系膜细胞表面标记物阻碍了这一过程。本研究的目的是鉴定系膜标记物并开发一种用于靶向肾小球的药物递送系统。基于文献，选择表达于肾小球系膜细胞表面的α 8（α8）整合素作为递送的靶分子。本文研究了两个狼疮性肾炎易感小鼠品系NZM 2328和NZM 2328 × NODF1。通过免疫荧光和QPCR证实正常和肾炎小鼠肾小球中α8整合素的表达。配制脂质体并与抗α8整联蛋白抗体缀合。这些免疫脂质体（IL）装载有DiI（一种红色荧光染料），以允许体内追踪，并注射到不同年龄的雌性小鼠的尾静脉中。通过荧光显微镜和流式细胞术研究靶向的特异性。α8整合素在正常和肾炎小鼠肾小球中均有表达。尾静脉注射抗α8整合素IL，运输至正常和肾炎小鼠的肾小球和肾小球系膜细胞。抗α8整合素IL的DiI递送具有组织特异性，主要针对肾小球，并被CD 11b细胞进行一些非特异性吸收。这是小鼠尾静脉注射后特异性递送至系膜的第一个证明。抗α8整合素IL为狼疮和其他肾小球疾病的靶向药物治疗提供了新的途径。
Glomerular mesangial cells are active participants in pathogenesis of lupus glomerulonephritis (GN). Thus, targeted delivery of therapeutics to mesangial cells would be an attractive approach to treatment. However, lack of unique mesangial cell surface markers has hampered this process. The objective of this study was to identify mesangial marker(s) and develop a system for targeted drug delivery to the glomerulus. Based on literature, alpha 8 (α8) integrin, expressed on surface of glomerular mesangial cells, was selected as a target molecule for delivery. Two mouse strains susceptible to lupus GN, NZM2328 and NZM2328×NOD F1 were studied. Glomerular expression of α8 integrin in normal and nephritic mice was confirmed by immunofluorescence and QPCR. Liposomes were formulated and conjugated with an anti-α8 integrin antibody. These immuno-liposomes (ILs) were loaded with DiI, a red fluorescent dye, to allow tracking in vivo and injected into the tail vein of female mice at different ages. Specificity of targeting was studied by fluorescence microscopy and flow cytometry. α8 integrin is expressed in glomeruli of normal and nephritic mice. Anti-α8 integrin ILs injected into the tail vein, traffic to the glomerulus and glomerular mesangial cells in normal and nephritic mice. The DiI delivery by anti-α8 integrin ILs was tissue specific, predominantly to glomeruli with some non-specific uptake by CD11b cells. This is the first demonstration of specific delivery to mesangium following tail vein injection in mice. The anti-α8 integrin ILs offer a novel approach for targeted drug therapy in lupus and other glomerular diseases.
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影响因子：
3.2
作者：
Wagner, TE;Frevert, CW;Schnapp, LM
通讯作者：
Schnapp, LM
DOI：
10.1073/pnas.93.24.14164
发表时间：
1996-11-26
影响因子：
11.1
作者：
Huwyler, J;Wu, DF;Pardridge, WM
通讯作者：
Pardridge, WM
影响因子：
4.4
作者：
Saxena, Vijay;Lienesch, Douglas W.;Singh, Ram Raj
通讯作者：
Singh, Ram Raj
DOI：
10.1083/jcb.111.3.1233
发表时间：
1990-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kramer RH;Cheng YF;Clyman R
通讯作者：
Clyman R
DOI：
10.1152/ajprenal.00391.2007
发表时间：
2008-03-01
影响因子：
4.2
作者：
Asgeirdottir, Sigridur A.;Zwiers, Peter J.;Kamps, Jan A. A. M.
通讯作者：
Kamps, Jan A. A. M.