Enhanced accumulation of long-circulating liposomes modified with the nucleosome-specific monoclonal antibody 2C5 in various tumours in mice: gamma-imaging studies
Enhanced accumulation of long-circulating liposomes modified with the nucleosome-specific monoclonal antibody 2C5 in various tumours in mice: gamma-imaging studies
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DOI：
10.1007/s00259-006-0139-x
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发表时间：
2006-10-01
影响因子：
9.1
通讯作者：
Torchilin, Vladimir P.
中科院分区：
文献类型：
--
作者：
Elbayoumi, Tamer A.;Torchilin, Vladimir P.
目的：通过偶联具有核小体限制性活性的抗癌单克隆抗体2C5，进一步提高长循环脂质体对显像剂的肿瘤靶向性和递送能力，该抗体可以识别多种肿瘤表面但不能识别正常细胞，并且可以在体外和体内特异性地将药物载体靶向肿瘤细胞。方法：将2C5抗体用后插入技术将抗体修饰后，通过后插入技术附着在长循环脂质体（LCL）的表面。单末端活化的 PEG-脂质衍生物产生核小体特异性肿瘤靶向脂质体。使用荧光标记的脂质体，通过荧光显微镜和流式细胞术在几种细胞系中验证靶向脂质体的肿瘤细胞结合。 In-111-放射性标记的脂质体制剂（使用膜锚定螯合基团制备）用于通过直接伽马闪烁扫描检查脂质体的体内生物分布和肿瘤积累。结果：2C5抗体修饰的LCL证明体外特异性细胞与不同来源的各种癌细胞系的结合增加了三到八倍。与对照制剂相比，In-111 标记的肿瘤靶向脂质体显示出更长的循环时间和双倍的肿瘤积累。植入不同肿瘤的小鼠的全身伽马闪烁显像显示，在测试的肿瘤模型中，与不含 2C5 的制剂相比，In-111-2C5-LCL 的体内肿瘤显像速度明显更快（2C5-LCL 注射后 6 小时，非特异性类似物注射后 24 小时）。结论：2C5 抗体修饰的 LCL 在各种肿瘤中有效且特异性地积聚，可作为显像剂的递送载体，从而实现快速高效的成像肿瘤可视化。
Purpose: To further improve tumour targeting and delivery of imaging agents by long-circulating liposomes via the coupling of the anti-cancer monoclonal antibody 2C5 with nucleosome-restricted activity, which can recognize the surface of various tumours but not normal cells and can specifically target pharmaceutical carriers to tumour cells in vitro and in vivo.Methods: The 2C5 antibody was attached to the surface of long-circulating PEG-liposomes (LCL) by the post-insertion technique after antibody modification with a single-terminus activated PEG-lipid derivative to yield nucleosome-specific tumour-targeted liposomes. Tumour cell binding of the targeted liposomes was verified both by fluorescence microscopy and by flow cytometry in several cell lines using fluorescently labelled liposomes. In-111-radiolabelled liposomal formulations (prepared using membrane-anchored chelating groups) were used to examine in vivo biodistribution and tumour accumulation of liposomes by direct gamma scintigraphy.Results: The 2C5 antibody-modified LCL demonstrated a three- to eightfold increase in in vitro specific cell binding to various cancer cell lines of diverse origin. In-111-labelled tumour-targeted liposomes demonstrated prolonged circulation and doubled tumour accumulation compared with that of control formulations. Whole-body gamma scintigraphic imaging of mice implanted with different tumours revealed markedly faster (6 h post injection for 2C5-LCL vs 24 h for non-specific analogues) and superior in vivo tumour visualization with In-111-2C5-LCL than with the 2C5-free formulations in tested tumour models.Conclusion: The 2C5 antibody-modified LCL effectively and specifically accumulate in various tumours and can serve as delivery vehicles for imaging agents, allowing for fast and efficient tumour visualization.