Anti-neovascular therapy by liposomal DPP-CNDAC targeted to angiogenic vessels
Anti-neovascular therapy by liposomal DPP-CNDAC targeted to angiogenic vessels
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DOI：
10.1016/s0014-5793(02)02821-1
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发表时间：
2002-06-05
期刊：
影响因子：
3.5
通讯作者：
Oku, N
中科院分区：
文献类型：
--
作者：
Asai, T;Shimizu, K;Oku, N
我们先前报道了脂质体化的5 ′-O-二棕榈酰磷脂酰2 ′-C-氰基-2 ′-脱氧-1-β-D-阿拉伯呋喃戊糖基胞嘧啶（DPP-CNDAC），一种新型抗肿瘤核苷CNDAC的亲水化衍生物，对癌症治疗非常有用。另一方面，对于抗新生血管治疗，我们最近从噬菌体展示的随机肽库中分离出归巢于血管生成血管的肽，并观察到肽修饰的脂质体阿霉素强烈抑制肿瘤生长，可能是通过破坏血管生成内皮细胞。在本研究中，我们用血管生成归巢肽之一APRPG修饰DPP-CNDAC-脂质体，并检测其抗肿瘤活性。与相同剂量的未修饰的DPP-CNDAC-脂质体相比，三个剂量的APRPG修饰的DPP-CNDAC-脂质体（15 mg/kg，作为CNDAC）强烈抑制肿瘤生长。寿命延长了31.8%，6只小鼠中有1只完全治愈。由于脂质体在肿瘤组织中的积累在APRPG-脂质体和未修饰的脂质体之间没有太大的差异，因此增强的治疗功效可以解释为靶标的改变，即APRPG-修饰的DPP-CNDAC-脂质体通过损伤血管生成内皮细胞引起肿瘤生长抑制。抗新生血管治疗承诺没有耐药性，并且应该对基本上任何种类的实体瘤有效;因此，目前的结果证明了该治疗的另一个益处，即癌症治疗的高功效。(C)2002年由Elsevier Science B. V.代表欧洲生物化学学会联合会出版。
We previously reported that liposomalized 5'-O-dipalmitoylphosphatidyl 2'-C-cyano-2'-deoxy-1-beta-D-arabinopentofuranosylcytosine (DPP-CNDAC), a hydropbobized derivative of the novel antitumor nucleoside CNDAC, is quite useful for cancer therapy. On the other hand, for anti-neovascular therapy, we recently isolated peptides homing to angiogenic vessels from a phage-displayed random peptide library, and observed that peptide-modified liposomal adriamycin strongly suppressed tumor growth, perhaps through damaging angiogenic endothelial cells. In the present study, we modified DPP-CNDAC-liposomes with one of the angiogenic homing peptides, APRPG, and examined their antitumor activity. Three doses of APRPG-modified DPP-CNDAC-liposomes (15 mg/kg as CNDAC) strongly inhibited tumor growth compared with the same number of doses of unmodified DPP-CNDAC-liposomes. The life span was increased 31.8%, with one completely cured mouse out of the six mice treated. Since the accumulation of liposomes in the tumor tissue was not so much different between APRPG-liposomes and non-modified liposomes, the enhanced therapeutic efficacy may be explained as the alteration of targets, i.e. APRPG-modified DPP-CNDAC-liposomes caused tumor growth suppression through damage of angiogenic endothelial cells. Anti-neovascular therapy promises no drug resistance, and should be effective against essentially any kind of solid tumor; and thus the present results demonstrate another benefit of the therapy, namely, high efficacy of cancer treatment. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.