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Target-or-Clear Zirconium-89 Labeled Silica Nanoparticles for Enhanced Cancer-Directed Uptake in Melanoma: A Comparison of Radiolabeling Strategies
Chemistry of Materials ( IF 8.6 ) Pub Date : 2017-09-22 00:00:00 , DOI: 10.1021/acs.chemmater.7b02567
Feng Chen 1 , Kai Ma 2 , Li Zhang 1 , Brian Madajewski 1 , Pat Zanzonico 3 , Sonia Sequeira 4 , Mithat Gonen 5 , Ulrich Wiesner 2 , Michelle S. Bradbury 1, 6
Affiliation  

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.

中文翻译:

目标或清除锆89标记的二氧化硅纳米颗粒增强黑色素瘤的癌症定向摄取:放射标记策略的比较。

长期以来,设计具有高目标背景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,我们介绍一个“目标明确”的多功能纳米粒子平台,该平台展示了高的肿瘤靶向效率和保留率,同时最大程度地降低了脱靶效应。在微调放射性碘化(124 I,t 1/2 = 100.2 h)超小cRGDY共轭荧光二氧化硅纳米颗粒(C点)的表面化学性质后获得的有利的临床前和临床药代动力学特性的鼓舞下,我们试图研究其生物学特性如何。放射性金属如锆89(89 Zr,t1/2 = 78.4 h)使用两种不同的策略: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89 Zr与较新的表面胺化整联蛋白靶向C'点相连,从而在人黑素瘤模型中产生了良好的药代动力学和清除率,以及较高的肿瘤吸收率和靶标与背景之比在保持粒径低于有效肾小球滤过粒径截止值<10 nm的同时,将其保留给生物对照。纳米共轭物还根据其放射稳定性和血浆停留半衰期进行了表征。我们的89Zr标记的超小型有机无机杂化粒子是一种临床上很有前途的正电子发射断层显像示踪剂,具有适合增强的分子靶向癌症成像应用的放射生物学特性。
更新日期:2017-09-22
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