使用磷脂锚定叶酸-聚乙二醇共轭物对脂质体包裹药物进行肿瘤细胞靶向

Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates.

作者信息

Gabizon Alberto, Shmeeda Hilary, Horowitz Aviva T, Zalipsky Samuel

机构信息

Oncology Department, Shaare Zedek Medical Center, Hebrew University School of Medicine, Jerusalem, Israel.

出版信息

Adv Drug Deliv Rev. 2004 Apr 29;56(8):1177-92. doi: 10.1016/j.addr.2004.01.011.

Abstract

Targeting of liposomes with phospholipid-anchored folate conjugates is an attractive approach to deliver chemotherapeutic agents to folate receptor (FR) expressing tumors. The use of polyethylene glycol (PEG)-coated liposomes with folate attached to the outer end of a small fraction of phospholipid-anchored PEG molecules appears to be the most appropriate way to combine long-circulating properties critical for liposome deposition in tumors and binding of liposomes to FR on tumor cells. Although a number of important formulation parameters remain to be optimized, there are indications, at least in one ascitic tumor model, that folate targeting shifts intra-tumor distribution of liposomes to the cellular compartment. In vitro, folate targeting enhances the cytotoxicity of liposomal drugs against FR-expressing tumor cells. In vivo, the therapeutic data are still fragmentary and appear to be formulation- and tumor model-dependent. Further studies are required to determine whether folate targeting can confer a clear advantage in efficacy and/or toxicity to liposomal drugs.

摘要

用磷脂锚定的叶酸共轭物靶向脂质体是一种将化疗药物递送至表达叶酸受体(FR)的肿瘤的有吸引力的方法。使用聚乙二醇(PEG)包被的脂质体,叶酸连接在一小部分磷脂锚定的PEG分子的外端,这似乎是将对脂质体在肿瘤中沉积至关重要的长循环特性与脂质体与肿瘤细胞上的FR结合相结合的最合适方法。尽管许多重要的制剂参数仍有待优化,但至少在一种腹水肿瘤模型中有迹象表明叶酸靶向将脂质体在肿瘤内的分布转移至细胞区室。在体外,叶酸靶向增强了脂质体药物对表达FR的肿瘤细胞的细胞毒性。在体内,治疗数据仍然不完整,并且似乎取决于制剂和肿瘤模型。需要进一步研究以确定叶酸靶向是否能在疗效和/或毒性方面赋予脂质体药物明显优势。

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