In vivo tumor vasculature targeted PET/NIRF imaging with TRC105(Fab)-conjugated, dual-labeled mesoporous silica nanoparticles.

In vivo tumor vasculature targeted PET/NIRF imaging with TRC105(Fab)-conjugated, dual-labeled mesoporous silica nanoparticles.
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DOI:
10.1021/mp500306k
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发表时间:
2014-11-03
影响因子:
4.9
通讯作者:
Cai W
Cai W
中科院分区:
医学2区
文献类型:
--
作者:
Chen F;Nayak TR;Goel S;Valdovinos HF;Hong H;Theuer CP;Barnhart TE;Cai W

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多功能介孔二氧化硅纳米粒子(MSN)具有良好的集成多模态成像性能,在过去的十年中产生了越来越多的研究兴趣。然而,在开发基于MSN的多模态成像剂来对肿瘤进行成像方面取得的进展有限。我们描述了成功的共轭,铜-64(64 Cu,t1/2 = 12.7 h),800 CW(近红外荧光[NIRF]染料)和TRC 105(人/鼠嵌合IgG 1单克隆抗体)通过成熟的表面工程方法结合到MSN表面,产生用于肿瘤脉管系统的体内靶向正电子发射断层摄影术(PET)成像/NIRF成像的双标记MSN。通过各种体外、体内和离体实验,全面研究了4 T1小鼠乳腺肿瘤荷瘤小鼠的药代动力学和肿瘤靶向疗效/特异性。双标记MSN是未来癌症治疗诊断学的有吸引力的候选者。
Multifunctional mesoporous silica nanoparticles (MSN) with well-integrated multimodality imaging properties have generated increasing research interest in the past decade. However, limited progress has been made in developing MSN-based multimodality imaging agents to image tumors. We describe the successful conjugation of, copper-64 (64Cu, t1/2 = 12.7 h), 800CW (a near-infrared fluorescence [NIRF] dye), and TRC105 (a human/murine chimeric IgG1 monoclonal antibody) to the surface of MSN via well-developed surface engineering procedures, resulting in a dual-labeled MSN for in vivo targeted positron emission tomography (PET) imaging/NIRF imaging of the tumor vasculature. Pharmacokinetics and tumor targeting efficacy/specificity in 4T1 murine breast tumor-bearing mice were thoroughly investigated through various in vitro, in vivo, and ex vivo experiments. Dual-labeled MSN is an attractive candidate for future cancer theranostics.
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