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一种由重组两亲嵌段多肽构成的 NGR 修饰胶束在体内的肿瘤靶向性。

In vivo tumor targeting by a NGR-decorated micelle of a recombinant diblock copolypeptide.

机构信息

Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.

出版信息

J Control Release. 2011 Oct 30;155(2):144-51. doi: 10.1016/j.jconrel.2011.06.044. Epub 2011 Jul 8.


DOI:10.1016/j.jconrel.2011.06.044
PMID:21763734
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3196042/
Abstract

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.

摘要

抗血管靶向治疗是一种很有前途的肿瘤治疗策略。这种策略有可能克服与实体瘤中靶向肿瘤细胞相关的许多传输障碍,因为肿瘤血管系统直接可用于全身循环中的靶向药物。我们报告了一种由多价聚合物胶束组成的新型纳米级递药系统,该系统靶向在肿瘤血管系统和血管周围细胞中优先上调的受体,特别是 CD13。为此,我们利用了由基因工程弹性蛋白样多肽(ELP)组成的两亲嵌段共聚物,该共聚物自组装成单分散的球形胶束。这些聚合物胶束通过在其冠部掺入靶向 CD13 受体的 NGR 三肽配体进行功能化。我们研究了这些 NGR 功能化纳米颗粒的自组装和体内肿瘤靶向性,并表明通过胶束自组装多价呈现 NGR 可通过靶向 CD13 选择性地靶向肿瘤血管系统。此外,与正常组织相比,我们发现纳米颗粒在肿瘤组织中的血管保留和血管外积累更多,尽管增强程度不大。这些结果表明,通过用多价配体呈现纳米颗粒靶向肿瘤血管系统中上调的受体,可以实现对实体瘤的增强递药,但需要进一步的工作来优化此类多价靶向系统。

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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
The effects of particle size and molecular targeting on the intratumoral and subcellular distribution of polymeric nanoparticles.

Mol Pharm. 2010-8-2

[2]
Morphing low-affinity ligands into high-avidity nanoparticles by thermally triggered self-assembly of a genetically encoded polymer.

ACS Nano. 2010-4-27

[3]
Temperature triggered self-assembly of polypeptides into multivalent spherical micelles.

J Am Chem Soc. 2008-1-16

[4]
Functionalized micellar systems for cancer targeted drug delivery.

Pharm Res. 2007-6

[5]
cNGR: a novel homing sequence for CD13/APN targeted molecular imaging of murine cardiac angiogenesis in vivo.

Arterioscler Thromb Vasc Biol. 2006-12

[6]
Polymer conjugates as anticancer nanomedicines.

Nat Rev Cancer. 2006-9

[7]
Evaluation of an elastin-like polypeptide-doxorubicin conjugate for cancer therapy.

J Control Release. 2003-8-28

[8]
Self-assembly of block copolymers derived from elastin-mimetic polypeptide sequences.

Adv Drug Deliv Rev. 2002-10-18

[9]
Polymer vesicles.

Science. 2002-8-9

[10]
Block copolymer micelles for delivery of gene and related compounds.

Adv Drug Deliv Rev. 2002-2-21

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