Recent advances in tumor-targeting anticancer drug conjugates

被引:445
作者
Jaracz, S
Chen, J
Kuznetsova, LV
Ojima, L [1 ]
机构
[1] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Inst Chem Biol & Drug Discovery, Stony Brook, NY 11794 USA
关键词
tumor-targeting; drug delivery; monoclonal antibody; polyunsaturated fatty acids; folic acid; hyaluronic acid; conjugate; liposome; cytotoxic; chemotherapy;
D O I
10.1016/j.bmc.2005.04.084
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Traditional cancer chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing severe undesirable side effects. Therefore, various drug delivery protocols and systems have been explored in the last three decades. Tumor cells overexpress many receptors and biomarkers, which can be used as targets to deliver cytotoxic agents into tumors. In general, a tumor-targeting drug delivery system consists of a tumor recognition moiety and a cytotoxic warhead connected directly or through a suitable linker to form a conjugate. The conjugate, which can be regarded as 'prodrug', should be systemically nontoxic. This means that the linker must be stable in circulation. Upon internalization into the cancer cell the conjugate should be readily cleaved to regenerate the active cytotoxic agent. Tumor-targeting conjugates bearing cytotoxic agents can be classified into several groups based on the type of cancer recognition moieties. This review describes recent advances in tumor-targeting drug conjugates including monoclonal antibodies, polyunsaturated fatty acids, folic acid, hyaluronic acid, and oligopeptides as tumor-targeting moieties. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5043 / 5054
页数:12
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