本期Nature Communications上發(fā)表的一篇研究論文報告了能將藥物定位到癌癥組織上的一個多用途化學(xué)標簽,。該標簽（理論上能被附著到各種現(xiàn)有抗癌藥物上,，并能被不同類型的與腫瘤相關(guān)的酶通過兩個步驟除掉）也許能增強抗癌療法的療效。
Nobuhide Ueki及同事報告說,，需要兩種酶來除掉該標簽和釋放藥物,，藥物預(yù)計主要在癌變組織中出現(xiàn)。組蛋白脫乙酰酶通過將乙?；鶑牡鞍咨铣魜砜刂苹虮磉_,，并且在腫瘤中經(jīng)常是有活性的；Cathepsin L也已被發(fā)現(xiàn)與腫瘤發(fā)展和轉(zhuǎn)移相關(guān),。通過組蛋白脫乙酰酶將一個乙?；鶑倪@個標簽上除掉,，會將一個結(jié)合點暴露出來，后者允許隨后被Cathepsin L劈分,。作者將該標簽附著到抗癌藥物“嘌呤霉素”上,，發(fā)現(xiàn)帶標簽的“嘌呤霉素”在一個結(jié)腸癌動物模型中在抑制腫瘤生長方面比不帶標簽的藥物更有效。（生物谷Bioon.com）
生物谷推薦的英文摘要
Nature Communications doi:10.1038/ncomms3735
Selective cancer targeting with prodrugs activated by histone deacetylases and a tumour-associated protease
Nobuhide UekiSiyeon LeeNicole S. SampsonMichael J. Hayman
Eradication of cancer cells while minimizing damage to healthy cells is a primary goal of cancer therapy. Highly selective drugs are urgently needed. Here we demonstrate a new prodrug strategy for selective cancer therapy that utilizes increased histone deacetylase (HDAC) and tumour-associated protease activities produced in malignant cancer cells. By coupling an acetylated lysine group to puromycin,， a masked cytotoxic agent is created,， which is serially activated by HDAC and an endogenous protease cathepsin L (CTSL) that remove the acetyl group first and then the unacetylated lysine group liberating puromycin. The agent selectively kills human cancer cell lines with high HDAC and CTSL activities. In vivo studies confirm tumour growth inhibition in prodrug-treated mice bearing human cancer xenografts. This cancer-selective cleavage of the masking group is a promising strategy for the next generation of anticancer drug development that could be applied to many other cytotoxic agents.
