In vivo tumor targeting by a NGR-decorated micelle of a recombinant diblock copolypeptide.
In vivo tumor targeting by a NGR-decorated micelle of a recombinant diblock copolypeptide.
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DOI：
10.1016/j.jconrel.2011.06.044
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发表时间：
2011-10-30
期刊：
影响因子：
--
通讯作者：
Chilkoti A
中科院分区：
文献类型：
--
作者：
Simnick AJ;Amiram M;Liu W;Hanna G;Dewhirst MW;Kontos CD;Chilkoti A
抗血管靶向是一种有前途的肿瘤治疗策略。该策略有可能克服与靶向实体瘤中的肿瘤细胞相关的许多运输障碍，因为肿瘤脉管系统可直接进入体循环中的靶向载体。我们报告了一种新型纳米级递送系统，由多价聚合物胶束组成，靶向肿瘤脉管系统和血管周围细胞中优先上调的受体，特别是 CD13。为此，我们利用了两亲性嵌段共聚物，该共聚物由基因工程弹性蛋白样多肽（ELP）组成，可自组装成单分散球形胶束。这些聚合物胶束通过在其冠上结合 NGR 三肽配体（其靶向 CD13 受体）而实现功能化。我们检查了这些 NGR 功能化纳米粒子的自组装和体内肿瘤靶向性，结果表明，胶束自组装产生的 NGR 多价呈现通过靶向 CD13 选择性地靶向肿瘤脉管系统。此外，与正常组织相比，我们发现肿瘤组织中纳米粒子的血管保留和血管外积累更大，尽管增强程度不大。这些结果表明，通过用多价配体呈递纳米颗粒靶向肿瘤脉管系统中上调的受体，可以增强对实体瘤的递送，但需要额外的工作来优化此类多价靶向系统。
Antivascular targeting is a promising strategy for tumor therapy. This strategy has the potential to overcome many of the transport barriers associated with targeting tumor cells in solid tumors, because the tumor vasculature is directly accessible to targeting vehicles in systemic circulation. We report a novel nanoscale delivery system consisting of multivalent polymer micelles to target receptors that are preferentially upregulated in the tumor vasculature and perivascular cells, specifically CD13. To this end we utilized amphiphilic block copolymers, composed of a genetically engineered elastin-like polypeptide (ELP) that self-assemble into monodisperse spherical micelles. These polymer micelles were functionalized by incorporating the NGR tripeptide ligand, which targets the CD13 receptor, on their corona. We examined the self-assembly and in vivo tumor targeting by these NGR-functionalized nanoparticles and show that multivalent presentation of NGR by micelle self-assembly selectively targets the tumor vasculature by targeting CD13. Furthermore, we show greater vascular retention and extravascular accumulation of nanoparticles in tumor tissue compared to normal tissue, although the enhancement is modest. These results suggest that enhanced delivery to solid tumors can be achieved by targeting upregulated receptors in the tumor vasculature with multivalent ligand presenting nanoparticles, but additional work is required to optimize such systems for multivalent targeting.
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影响因子：
14.5
作者：
Ruoslahti, E
通讯作者：
Ruoslahti, E
DOI：
10.1161/01.atv.0000245807.65714.0b
发表时间：
2006-12-01
影响因子：
8.7
作者：
Buehler, Alexandra;van Zandvoort, Marc A. M. J.;de Muinck, Ebo D.
通讯作者：
de Muinck, Ebo D.
影响因子：
20.3
作者：
Bhagwat, SV;Lahdenranta, J;Shapiro, LH
通讯作者：
Shapiro, LH
影响因子：
2.9
作者：
GILL, SC;VONHIPPEL, PH
通讯作者：
VONHIPPEL, PH
影响因子：
3.4
作者：
Hlavacek, WS;Posner, RG;Perelson, AS
通讯作者：
Perelson, AS