Flexible filaments for in vivo imaging and delivery: persistent circulation of filomicelles opens the dosage window for sustained tumor shrinkage.
Flexible filaments for in vivo imaging and delivery: persistent circulation of filomicelles opens the dosage window for sustained tumor shrinkage.
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DOI：
10.1021/mp900022m
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发表时间：
2009-09
影响因子：
4.9
通讯作者：
Discher DE
中科院分区：
文献类型：
--
作者：
Christian DA;Cai S;Garbuzenko OB;Harada T;Zajac AL;Minko T;Discher DE
合成载体的形状效应在很大程度上未在体内探索，尽管最近的研究结果表明，即使长度为微米，柔性细丝也可以持续存在于循环中。在此，为了更好地评估生物分布，将近红外荧光团（NIRF）掺入这种嵌段共聚物“丝状胶束”中，并且体内和离体成像均显示，这些蠕虫状胶束中的大多数在静脉内注射后保持在循环中至少一天。NIRF成像进一步表明，丝状胶束对流进入肿瘤，并且一些碎片可以渗透到肿瘤间质中。为了评估功能效应，将疏水性药物紫杉醇（tax）装载到相同共聚物的丝状胶束和超声产生的球形胶束中。静脉注射载紫杉醇的丝状胶束，与载紫杉醇的球形胶束相比，在正常小鼠中的最大耐受剂量几乎增加一倍。在荷瘤小鼠中，较高剂量的Tax产生更大和更持续的肿瘤缩小和肿瘤细胞凋亡。因此，这些结果开始解决非球形载体如何向实体瘤递送显像剂和抗癌治疗剂的机制。
Shape effects of synthetic carriers are largely unexplored in vivo, although recent findings suggest that flexible filaments can persist in the circulation even if microns in length. Here, to better assess biodistribution, a near infrared fluorophore (NIRF) was incorporated into such block copolymer ‘filomicelles’, and both in vivo and ex vivo imaging show that the majority of these worm-like micelles remain in the circulation for at least a day after intravenous injection. NIRF imaging further suggests that filomicelles convect into a tumor and some fragments can penetrate into the tumor stroma. To assess a functional effect, the hydrophobic drug paclitaxel (tax) was loaded into both filomicelles and sonication-generated spherical micelles of the same copolymer. Intravenous injection of tax-loaded filomicelles nearly doubles the maximum tolerated dose of tax in normal mice compared to tax-loaded spherical micelles. In tumor-bearing mice, the higher dose of tax produces greater and more sustained tumor shrinkage and tumor cell apoptosis. These results thus begin to address mechanisms for how non-spherical carriers deliver both imaging agents and anti-cancer therapeutics to solid tumors.
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影响因子：
10.8
作者：
Champion, Julie A.;Katare, Yogesh K.;Mitragotri, Samir
通讯作者：
Mitragotri, Samir
影响因子：
11.5
作者：
Kim, TY;Kim, DW;Bang, YJ
通讯作者：
Bang, YJ
影响因子：
15
作者：
Geng, Y;Discher, DE
通讯作者：
Discher, DE
DOI：
10.1073/pnas.0702576104
发表时间：
2007-10-02
影响因子：
11.1
作者：
Pajerowski, J. David;Dahl, Kris Noel;Discher, Dennis E.
通讯作者：
Discher, Dennis E.
影响因子：
3.7
作者：
Cai, Shenshen;Vijayan, Kandaswamy;Discher, Dennis E.
通讯作者：
Discher, Dennis E.