Enhancement of anticancer activity in antineovascular therapy is based on the intratumoral distribution of the active targeting carrier for anticancer drugs.
Enhancement of anticancer activity in antineovascular therapy is based on the intratumoral distribution of the active targeting carrier for anticancer drugs.
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DOI：
10.1248/bpb.29.1936
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发表时间：
2006-09
影响因子：
2
通讯作者：
N. Maeda;S. Miyazawa;K. Shimizu;T. Asai;S. Yonezawa;S. Kitazawa;Y. Namba;H. Tsukada;N. Oku
中科院分区：
文献类型：
--
作者：
N. Maeda;S. Miyazawa;K. Shimizu;T. Asai;S. Yonezawa;S. Kitazawa;Y. Namba;H. Tsukada;N. Oku
我们之前观察到，由于 APRPG 肽被用作血管生成内皮的主动靶向工具，封装在 Ala-Pro-Arg-Pro-Gly-聚乙二醇修饰脂质体 (APRPG-PEG-Lip) 中的抗癌药物在荷瘤小鼠中具有增强的抗癌功效。这种抗血管疗法（ANET）旨在通过破坏血管生成血管来间接消灭肿瘤细胞。在本研究中，我们利用正电子发射断层扫描（PET）检查了[2-（18）F]2-氟-2-脱氧-D-葡萄糖（[2-（18）F]FDG）标记的APRPG-PEG-Lip的体内运输，并观察到该脂质体的运输与非靶向长循环脂质体（PEG-Lip）的运输非常相似。然后，使用荧光标记的脂质体对两种脂质体的瘤内分布进行组织化学分析。与体内运输相比，两种类型的脂质体的肿瘤内分布有很大不同：APRPG-PEG-Lip 与经过 CD31 免疫组织化学染色的血管生成内皮细胞共定位，尽管 PEG-Lip 位于血管生成血管周围。这些结果强烈表明，药物载体的肿瘤内分布对于治疗效果比抗癌药物在肿瘤中的总积累重要得多，并且抗癌药物主动递送至血管生成血管对于癌症治疗是有用的。
We previously observed the enhanced anticancer efficacy of anticancer drugs encapsulated in Ala-Pro-Arg-Pro-Gly-polyethyleneglycol-modified liposome (APRPG-PEG-Lip) in tumor-bearing mice, since APRPG peptide was used as an active targeting tool to angiogenic endothelium. This modality, antineovascular therapy (ANET), aims to eradicate tumor cells indirectly through damaging angiogenic vessels. In the present study, we examined the in vivo trafficking of APRPG-PEG-Lip labeled with [2-(18)F]2-fluoro-2-deoxy-D-glucose ([2-(18)F]FDG) by use of positron emission tomography (PET), and observed that the trafficking of this liposome was quite similar to that of non-targeted long-circulating liposome (PEG-Lip). Then, histochemical analysis of intratumoral distribution of both liposomes was performed by use of fluorescence-labeled liposomes. In contrast to in vivo trafficking, intratumoral distribution of both types of liposomes was quite different: APRPG-PEG-Lip was colocalized with angiogenic endothelial cells that were immunohistochemically stained for CD31, although PEG-Lip was localized around the angiogenic vessels. These results strongly suggest that intratumoral distribution of drug carrier is much more important for therapeutic efficacy than the total accumulation of the anticancer drug in the tumor, and that active delivery of anticancer drugs to angiogenic vessels is useful for cancer treatment.