Enhanced distribution of NK012, a polymeric micelle-encapsulated SN-38, and sustained release of SN-38 within tumors can beat a hypovascular tumor
Enhanced distribution of NK012, a polymeric micelle-encapsulated SN-38, and sustained release of SN-38 within tumors can beat a hypovascular tumor
复制标题
DOI：
10.1111/j.1349-7006.2008.00806.x
复制
发表时间：
2008-06-01
期刊：
影响因子：
5.7
通讯作者：
Matsumura, Yasuhiro
中科院分区：
文献类型：
--
作者：
Saito, Yohei;Yasunaga, Masahiro;Matsumura, Yasuhiro
人类胰腺癌通常是低血供的，并且富含氚。这些病理屏障可能通过结合抗癌剂在整个肿瘤组织中的渗透而导致胰腺癌的难治性。本研究的目的是确定NK 012是否是治疗少血管肿瘤的合适制剂。在胰腺肿瘤异种移植物中，PSN 1似乎具有最丰富的肿瘤血管和最少数量的基质细胞和基质。相比之下，Capan 1具有最差的肿瘤血管和最丰富的基质组织。荧光显微镜和高效液相色谱分析表明，尽管NK 012在两种肿瘤的整个体内积累并持续分布超过48 h，但CPT-11在6 h内几乎完全从两种肿瘤中消失。此外，在NK 012给药后，SN-38的有效缓释在两种肿瘤中维持超过96小时。CPT-11给药后，在Capan 1肿瘤中24小时后或在PSN 1肿瘤中48小时后不再检测到SN-38。在用NK 012治疗的小鼠中所有肿瘤都被根除，但在用CPT-11治疗的小鼠中没有。由于SN-38的抗肿瘤活性是时间依赖性的，NK 012结合了SN-38在肿瘤内的增强分布和持续释放，可能是治疗少血管肿瘤（如胰腺癌）的理想药物。
Human pancreatic cancer is generally hypovascular in nature and rich in interstitium. These pathological barriers may contribute to the intractable nature of pancreatic cancer by binding the penetration of anticancer agents throughout the tumor tissue. The aim of the present study was to determine whether NK012 is an appropriate formulation for the treatment of hypovascular tumors. Among pancreatic tumor xenografts, PSN1 appeared to have the richest tumor vasculature and the least number of stromal cells and matrix. In contrast, Capan1 had the poorest tumor vasculature and most abundant stromal tissue. Fluorescence microscopy and high-performance liquid chromatography analysis demonstrated that although NK012 accumulated and continued to be distributed for more than 48 h throughout the entire body of both tumors, CPT-11 disappeared almost entirely from both tumors within 6 h. In addition, efficient sustained release of SN-38 was maintained for more than 96 h in both tumors following administration of NK012. Following the administration of CPT-11, SN-38 was no longer detectable after 24 h in the Capan1 tumor or after 48 h in the PSN1 tumor. All tumors were eradicated in the mice treated with NK012 but not in those treated with CPT-11. Because the antitumor activity of SN-38 is time dependent, NK012, which combines enhanced distribution with sustained release of SN-38 within tumors, may be ideal for the treatment of hypovascular tumors, such as pancreatic cancer.