Evaluation of Multivalent, Functional Polymeric Nanoparticles for Imaging Applications

被引：80

作者：

Shokeen, Monica ^{[4
]}

Pressly, Eric D. ^{[1
,2
]}

Hagooly, Aviv ^{[4
]}

Zheleznyak, Alexander ^{[4
]}

Ramos, Nicholas ^{[4
]}

Fiamengo, Ashley L. ^{[4
]}

Welch, Michael J. ^{[4
,6
]}

Hawker, Craig J. ^{[1
,2
,3
]}

Anderson, Carolyn J. ^{[4
,5
,6
]}

机构：

[1] Univ Calif Santa Barbara, Mat Res Lab, Santa Barbara, CA 93106 USA

[2] Univ Calif Santa Barbara, Dept Mat, Santa Barbara, CA 93106 USA

[3] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA

[4] Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA

[5] Washington Univ, Dept Chem, St Louis, MO 63110 USA

[6] Washington Univ, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA

来源：

ACS NANO | 2011年 / 5卷 / 02期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

polymeric nanoparticles; click chemistry; cellular uptake; pharmacokinetics; SELF-ASSEMBLED MONOLAYERS; IN-VIVO EVALUATION; RGD PEPTIDES; VITRO; BIODISTRIBUTION; DELIVERY; GLYCOL); DESIGN; MODEL;

D O I：

10.1021/nn102278w

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A series of multivalent, functional polymer nanoparticles with diagnostic/imaging units and targeting ligands for molecular targeting were synthesized with the loading of the chainend-functionalized GRGDS peptide targeting sequence (model system based on integrin alpha(v)beta(3)) ranging from 0 to 50%. Accurate structural and functional group control in these systems was achieved through a modular approach involving the use of multiple functionalized macromonomer/monomer units combined with living free radical polymerization. In cellulo results show an increase in uptake In alpha(v)beta(3) integrin-positive U87MG glioblastoma cells with increasing RGD loading and a possible upper limit on the effectiveness of the number of RGD peptides for targeting alpha(v)beta(3) Integrin. Significantly, this increased targeting efficiency is coupled with in vivo biodistribution results, which show decreased blood circulation and increased liver uptake with increasing RGD loading. The results demonstrate the importance of controlling ligand loading in order to achieve optimal performance for therapeutic and imaging applications for multivalent nanoparticle-based systems.

引用

页码：738 / 747

页数：10

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