Single-antibody, targeted nanoparticle delivery of camptothecin.
Single-antibody, targeted nanoparticle delivery of camptothecin.
复制标题
DOI：
10.1021/mp300702x
复制
发表时间：
2013-07-01
影响因子：
4.9
通讯作者：
Davis ME
中科院分区：
文献类型：
--
作者：
Han H;Davis ME
我们已经开发了一种新的组装靶向纳米颗粒的方法，该方法利用含有硼酸的靶向剂和具有二醇的聚合物-药物缀合物之间的络合作用。在这里，我们报告了通过这种新的组装方法形成的纳米颗粒的第一个体内抗肿瘤结果。在携带HER 2过表达BT-474人乳腺癌肿瘤的裸鼠中研究了由喜树碱（CPT）的粘酸聚合物缀合物MAP-CPT组成的纳米颗粒，平均含有一种赫赛汀抗体。非靶向MAP-CPT和含抗体的MAP-CPT纳米颗粒的约。30-40 nm直径和轻微负zeta电位显示在小鼠尾静脉注射后延长的体内循环和相似的生物分布。在小鼠中，发现非靶向和含赫赛汀的MAP-CPT纳米颗粒的最大耐受剂量（MTD）分别为10和8 mg CPT/kg。在研究结束时，与80 mg/kg伊立替康（平均肿瘤体积为575 mm 3）和8 mg/kg CPT（平均肿瘤体积为808 mm 3）相比，8 mg CPT/kg非靶向MAP-CPT纳米颗粒治疗的荷BT-474人乳腺肿瘤小鼠显示出显著的肿瘤生长抑制（平均肿瘤体积为63 mm 3）。5.9 mg/kg赫赛汀抗体治疗导致8只小鼠中的5只完全肿瘤消退，研究结束时平均肿瘤体积为60 mm 3。用1 mg CPT/kg的MAP-CPT纳米颗粒治疗的小鼠未显示肿瘤抑制。然而，接受MAP-CPT纳米颗粒（1 mg CPT/kg）给药的所有小鼠在研究结束时均显示出完全的肿瘤消退，该MAP-CPT纳米颗粒平均每个纳米颗粒含有一个赫赛汀分子（5.9 mg赫赛汀当量/kg）。这些结果表明，通过平均掺入单一抗体，可以增强携带抗癌药物的纳米颗粒的抗肿瘤功效。
We have developed a new method for assembling targeted nanoparticles that utilizes the complexation between targeting agents that contain boronic acids and polymer-drug conjugates that possess diols. Here, we report the first in vivo, antitumor results of a nanoparticle formed via this new assembly methodology. A nanoparticle consisting of a mucic acid polymer conjugate of camptothecin (CPT), MAP-CPT; and containing on average one Herceptin antibody is investigated in nude mice bearing HER2 overexpressing BT-474 human breast cancer tumors. Nontargeted MAP-CPT and antibody-containing MAP-CPT nanoparticles of ca. 30–40 nm diameter and slightly negative zeta potential show prolonged in vivo circulation and similar biodistributions after intravenous tail vein injections in mice. The maximum tolerated dose (MTD) of the nontargeted and Herceptin-containing MAP-CPT nanoparticles are found to be 10 and 8 mg CPT/kg, respectively, in mice. Mice bearing BT-474 human breast tumors treated with nontargeted MAP-CPT nanoparticles at 8 mg CPT/kg show significant tumor growth inhibition (mean tumor volume of 63 mm3) when compared to Irinotecan at 80 mg/kg (mean tumor volume of 575 mm3) and CPT at 8 mg/kg (mean tumor volume of 808 mm3) at the end of the study. Herceptin antibody treatment at 5.9 mg/kg results in complete tumor regressions in 5 out of 8 mice, with a mean tumor volume of 60 mm3 at the end of the study. Mice treated with MAP-CPT nanoparticles at 1 mg CPT/kg do not show tumor inhibition. However, all mice receiving administrations of MAP-CPT nanoparticles (1 mg CPT/kg) that contain on average a single Herceptin molecule per nanoparticle (5.9 mg Herceptin equivalent/kg) show complete tumor regression by the end of the study. These results demonstrate that the antitumor efficacy of nanoparticles carrying anticancer drugs can be enhanced by incorporating on average a single antibody.
登录
查看更多内容
影响因子：
45.3
作者：
Cobleigh, MA;Vogel, CL;Slamon, DJ
通讯作者：
Slamon, DJ
影响因子：
11.5
作者：
Homsi, Jade;Simon, George R.;Daud, Adil I.
通讯作者：
Daud, Adil I.
影响因子：
2.9
作者：
MI, ZH;BURKE, TG
通讯作者：
BURKE, TG
影响因子：
4.7
作者：
Han, Han;Davis, Mark E.
通讯作者：
Davis, Mark E.
影响因子：
45.3
作者：
Pro, Barbara;Advani, Ranjana;Shustov, Andrei
通讯作者：
Shustov, Andrei