Target-or-Clear Zirconium-89 Labeled Silica Nanoparticles for Enhanced Cancer-Directed Uptake in Melanoma: A Comparison of Radiolabeling Strategies.
Target-or-Clear Zirconium-89 Labeled Silica Nanoparticles for Enhanced Cancer-Directed Uptake in Melanoma: A Comparison of Radiolabeling Strategies.
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DOI：
10.1021/acs.chemmater.7b02567
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发表时间：
2017-10-10
期刊：
影响因子：
--
通讯作者：
Bradbury MS
中科院分区：
文献类型：
--
作者：
Chen F;Ma K;Zhang L;Madajewski B;Zanzonico P;Sequeira S;Gonen M;Wiesner U;Bradbury MS
设计具有高靶本底比的纳米材料平台一直是纳米医学领域的主要挑战之一。在这里，我们介绍了一种“靶向或清除”多功能纳米颗粒平台，该平台显示出高肿瘤靶向效率和保留率，同时最大限度地减少脱靶效应。在微调放射性碘化（124I, t1/2 = 100.2 h）超小crgdy共轭荧光二氧化硅纳米颗粒（C点）表面化学性质后，得到了良好的临床前和临床药代动力学特征，我们试图研究这些放射性偶联物的生物学特性如何受到放射性金属如锆-89 （89Zr, t1/2 = 78.4 h）偶联的影响，采用两种不同的策略：无螯合剂和基于螯合剂的放射性标记。使用两罐合成方法将89Zr附着在更新的、表面胺化的、靶向整合素的C '点上，在人类黑色素瘤模型中，与生物对照相比，具有良好的药代动力学和清除率，以及较高的肿瘤摄取和靶背景比，同时保持颗粒尺寸低于有效肾小球滤过尺寸的下限<10 nm。纳米缀合物的放射性稳定性和等离子体停留半衰期也被表征。我们的89zr标记的超小有机-无机杂化颗粒是一种临床上有前景的正电子发射断层扫描示踪剂，具有放射生物学特性，适合于增强分子靶向癌症成像应用。
Designing a nanomaterials platform with high target-to-background ratios has long been one of the major challenges in the field of nanomedicine. Here, we introduce a “target-or-clear” multifunctional nanoparticle platform that demonstrates high tumor-targeting efficiency and retention while minimizing off-target effects. Encouraged by the favorable preclinical and clinical pharmacokinetic profiles derived after fine-tuning surface chemical properties of radioiodinated (124I, t1/2 = 100.2 h) ultrasmall cRGDY-conjugated fluorescent silica nanoparticles (C dots), we sought to investigate how the biological properties of these radioconjugates could be influenced by the conjugation of radiometals such as zirconium-89 (89Zr, t1/2 = 78.4 h) using two different strategies: chelator-free and chelator-based radiolabeling. The attachment of 89Zr to newer, surface-aminated, integrin-targeting C′ dots using a two-pot synthesis approach led to favorable pharmacokinetics and clearance profiles as well as high tumor uptake and target-to-background ratios in human melanoma models relative to biological controls while maintaining particle sizes below the effective renal glomerular filtration size cutoff <10 nm. Nanoconjugates were also characterized in terms of their radiostability and plasma residence half-lives. Our 89Zr-labeled ultrasmall hybrid organic–inorganic particle is a clinically promising positron emission tomography tracer offering radiobiological properties suitable for enhanced molecularly targeted cancer imaging applications.
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工程本质上是锆-89放射性标记的自毁介孔二氧化硅纳米结构，用于体内生物分布和肿瘤靶向研究。
影响因子：
15.1
作者：
Goel, Shreya;Chen, Feng;Luan, Shijie;Valdovinos, Hector F.;Shi, Sixiang;Graves, Stephen A.;Ai, Fanrong;Barnhart, Todd E.;Theuer, Charles P.;Cai, Weibo
通讯作者：
Cai, Weibo
临床翻译的二氧化硅纳米颗粒作为以癌为标志性的探针进行图像引导的手术和干预措施。
DOI：
10.1039/c2ib20174g
发表时间：
2013-01
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Bradbury MS;Phillips E;Montero PH;Cheal SM;Stambuk H;Durack JC;Sofocleous CT;Meester RJ;Wiesner U;Patel S
通讯作者：
Patel S
影响因子：
16.6
作者：
Chen, Feng;Ellison, Paul A.;Lewis, Christina M.;Hong, Hao;Zhang, Yin;Shi, Sixiang;Hernandez, Reinier;Meyerand, M. Elizabeth;Barnhart, Todd E.;Cai, Weibo
通讯作者：
Cai, Weibo
影响因子：
3.1
作者：
Abou DS;Ku T;Smith-Jones PM
通讯作者：
Smith-Jones PM
影响因子：
10.8
作者：
Burns AA;Vider J;Ow H;Herz E;Penate-Medina O;Baumgart M;Larson SM;Wiesner U;Bradbury M
通讯作者：
Bradbury M