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抗癌治疗中的葡糖醛酸苷。

Glucuronides in anti-cancer therapy.

作者信息

Chen Xi, Wu Bingyuan, Wang Peng George

机构信息

Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.

出版信息

Curr Med Chem Anticancer Agents. 2003 Mar;3(2):139-50. doi: 10.2174/1568011033353470.

Abstract

Glucuronide prodrugs have shown promising efficacy in anti-cancer therapy due to their increased specificity and reduced systemic toxicity. The prodrugs can be used in prodrug monotherapy (PMT), which is based on elevated tumor beta-glucuronidase activity. beta-Glucuronidase activates the low-toxic prodrugs into highly cytotoxic agents specifically in the tumor site. The specificity of the prodrugs can be further improved by combined use with monoclonal antibodies against tumor-specific antigens, namely antibody-directed enzyme prodrug therapy (ADEPT); and the potency of the prodrugs can be greatly enhanced with the incorporation of an appropriate radionuclide in the combined chemo- and radio-therapy of cancer (CCRTC) strategy. The prodrugs can also be utilized to modify liposomes for efficient delivery of anti-cancer drugs.

摘要

葡糖醛酸酯前药因其特异性增强和全身毒性降低,在抗癌治疗中显示出有前景的疗效。这些前药可用于前药单一疗法(PMT),该疗法基于肿瘤β-葡糖醛酸酶活性升高。β-葡糖醛酸酶可将低毒前药特异性地激活为高细胞毒性剂,仅在肿瘤部位发挥作用。通过与针对肿瘤特异性抗原的单克隆抗体联合使用,即抗体导向酶前药疗法(ADEPT),可进一步提高前药的特异性;并且在癌症联合化疗和放疗(CCRTC)策略中,通过掺入适当的放射性核素,可大大增强前药的效力。前药还可用于修饰脂质体,以实现抗癌药物的高效递送。

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