Selective tumor cell targeting by the disaccharide moiety of bleomycin.
Selective tumor cell targeting by the disaccharide moiety of bleomycin.
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DOI：
10.1021/ja311090e
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发表时间：
2013-02-27
影响因子：
15
通讯作者：
Hecht, Sidney M.
中科院分区：
文献类型：
--
作者：
Yu, Zhiqiang;Schmaltz, Ryan M.;Bozeman, Trevor C.;Paul, Rakesh;Rishel, Michael J.;Tsosie, Krystal S.;Hecht, Sidney M.
在最近的一项研究中，研究人员在细胞培养中用多个BLM拷贝衍生的微泡研究了抗肿瘤药物博来霉素（BLM）的肿瘤靶向特性。结果表明，BLM选择性靶向MCF-7人乳腺癌细胞，而非“正常”乳腺细胞系MCF-10A。此外，BLM类似物去糖博莱霉素缺乏BLM的双糖部分，被发现对两种细胞系都没有靶向作用，这表明BLM的双糖部分是肿瘤选择性所必需的。在早期的研究中没有解决的问题是，单独的BLM双糖片段是否足以靶向肿瘤细胞，以及双糖是否可能被细胞摄取。在本研究中，我们将BLM、去糖BLM和BLM双糖偶联到菁染料Cy5**上。结果发现，BLM和BLM双糖偶联物选择性地结合到MCF-7细胞上，并被内化，而去糖BLM偶联物则没有。对于前列腺癌细胞系DU-145（正常的PZ-HPV-7前列腺细胞）和胰腺癌细胞系BxPC-3（正常的SVR A221a胰腺细胞）也是如此。该双糖在MCF-7和DU-145细胞中的靶向效率仅略低于BLM，在BxPC-3细胞中的靶向效率与BLM相当。这些结果表明，BLM双糖是肿瘤细胞靶向的必要和充分条件，这一发现对新型肿瘤显像和治疗剂的设计具有明显的意义。
In a recent study, the well documented tumor targeting properties of the antitumor agent bleomycin (BLM) were studied in cell culture using microbubbles that had been derivatized with multiple copies of BLM. It was shown that BLM selectively targeted MCF-7 human breast carcinoma cells, but not the “normal” breast cell line MCF-10A. Further, the BLM analogue deglycobleomycin, which lacks the disaccharide moiety of BLM, was found not to target either cell line, indicating that the BLM disaccharide moiety is necessary for tumor selectivity. Not resolved in the earlier study was the issue of whether the BLM disaccharide moiety alone is sufficient for tumor cell targeting, as well as the possible cellular uptake of the disaccharide. In the present study, we have conjugated BLM, deglycoBLM and BLM disaccharide to the cyanine dye Cy5**. It was found that the BLM and BLM disaccharide conjugates, but not the deglycoBLM conjugate, bound selectively to MCF-7 cells, and were internalized. The same was also true for the prostate cancer cell line DU-145 (but not for normal PZ-HPV-7 prostate cells) and for the pancreas cancer cell line BxPC-3 (but not for normal SVR A221a pancreas cells). The targeting efficiency of the disaccharide was only slightly less than that of BLM in MCF-7 and DU-145 cells, and comparable to BLM in BxPC-3 cells. These results establish that the BLM disaccharide is both necessary and sufficient for tumor cell targeting, a finding with obvious implications for the design of novel tumor imaging and therapeutic agents.
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影响因子：
19.7
作者：
BEKERMAN, C;MORAN, EM;GOTTSCHALK, A
通讯作者：
GOTTSCHALK, A
DOI：
10.1002/mpo.2950010104
发表时间：
1975-01-01
期刊：
Medical and Pediatric Oncology
影响因子：
--
作者：
JONES S E;LILIEN D L;SALMON S E
通讯作者：
SALMON S E
影响因子：
2.9
作者：
HOLMES, CE;CARTER, BJ;HECHT, SM
通讯作者：
HECHT, SM
影响因子：
15
作者：
Tao, Zhi-Fu;Konishi, Kazuhide;Hecht, Sidney M.
通讯作者：
Hecht, Sidney M.
影响因子：
15
作者：
Chapuis JC;Schmaltz RM;Tsosie KS;Belohlavek M;Hecht SM
通讯作者：
Hecht SM