Near-infrared emitting radioactive gold nanoparticles with molecular pharmacokinetics.
Near-infrared emitting radioactive gold nanoparticles with molecular pharmacokinetics.
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DOI：
10.1002/anie.201203031
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发表时间：
2012-10
影响因子：
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通讯作者：
Chen Zhou;G. Hao;P. Thomas;Jinbin Liu;Mengxiao Yu;Shasha Sun;Orhan K Öz;Xiankai Sun;Jie Zheng-Jie-Zh
中科院分区：
文献类型：
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作者：
Chen Zhou;G. Hao;P. Thomas;Jinbin Liu;Mengxiao Yu;Shasha Sun;Orhan K Öz;Xiankai Sun;Jie Zheng-Jie-Zh
临床使用的造影剂通常表现出以下药代动力学特征：全身给药后扩散迅速（分布半衰期t1/2α短），血液循环时间相对较长（消除半衰期t1/2β长），体内非特异性蓄积很少（肾可清除）。[1]这些特定的药代动力学特征不仅确保了临床成像过程的成功，而且最大限度地减少了造影剂引入引起的潜在健康危害。例如，99 mTc-SQ 30217（单光子发射计算机断层扫描（SPECT）成像剂），[2] 18F标记的氟乙酸盐（[18F] FAc）（一种高潜力的正电子发射断层扫描（PET）成像剂），[3]和碘美普尔（市售的X射线计算机断层扫描（CT）造影剂）[4]在约1.2分钟、9.0分钟和16.2分钟的1/2α和约10.1小时的1/2β处显示，静脉注射后11.3 h和2.34 h。虽然这些基于小分子的造影剂已被广泛使用或在临床中具有巨大的潜力，但一个主要的限制是它们仅适用于单模态成像。因此，不同成像技术的优势很难整合在一起，以更好地管理疾病。为了应对这一挑战，在过去的几十年中，人们一直致力于开发多模态成像探头。[5]一种通用的方法是使用优雅的合成策略将不同的功能性小分子整合在一起。[5d例如，Banerjee等人报道了一种基于小分子的双模态SPECT/近红外荧光（NIRF）成像剂，其在前列腺特异性膜抗原（PSMA）阳性异种移植物中显示出高的特异性摄取，以及用于体内靶向PSMA的优异的药代动力学。[5d]作为平行方向，基于纳米颗粒（NP）的多模态成像探针也引起了极大的关注，因为无机NP通常表现出大的表面/体积比、可调的和多样的材料性质。[5e例如，用64 Cu标记的放射性量子点（QD）已经用于荧光和PET成像。[8]Lin等人开发了分别用于光学和磁共振成像（MRI）的稳健的发光和顺磁性混合二氧化硅NP。[5a]金纳米颗粒（AuNPs）不仅可以在体外暗场、拉曼和光热成像中用作非光漂白发射体，[9]还可以用于增强体内光声和计算机断层扫描成像的对比度。[10]虽然这些令人兴奋的生物医学应用正在不断推动新型多模态纳米探针的出现，但无机纳米颗粒通常表现出与小分子造影剂不同的药代动力学。例如，碳纳米管[11]和氧化铁纳米颗粒[12]仅显示出短的一阶指数血液循环，静脉注射后半衰期分别为约1.0小时和约0.12小时。此外，网状内皮系统（RES）器官通常快速地隔离这些纳米结构，导致缓慢的RES清除过程和潜在的健康危害。[7g 9 c，13] NP的药代动力学的这些限制显著阻碍了它们的临床应用。因此，非常需要开发具有适合于不同成像技术的不同材料性质并且还表现出最佳体内药代动力学的纳米探针。纳米探针的生物分布、肾清除率和药代动力学主要取决于其粒径和表面。[14]例如，小于5 nm的多功能二氧化硅基颗粒可以有效地逃避网状内皮系统（RES）的摄取。[14e]除了...
Contrast agents used in clinics often exhibit the following pharmacokinetics: rapid diffusion (short distribution half-life t1/2α), relatively long blood circulation time (long elimination half-life t1/2β), and little nonspecific accumulation in the body (renal clearable) after systemic administration.[1] These specific pharmacokinetic features not only ensure the success of clinical imaging processes but also minimize the potential health hazards caused by the introduction of contrast agents. For example, 99mTc-SQ30217 (a single-photon emission computed tomography (SPECT) imaging agent),[2] 18F-labeled fluoroacetate ([18F] FAc)(a highly potential positron emission tomography (PET) imaging agent),[3] and Iomeprol (a commercially available X-ray computed tomography (CT) contrast agent)[4] exhibit at 1/2α of about 1.2 min, 9.0 min, and 16.2 min, and at 1/2β of about 10.1 h, 11.3 h, and 2.34 h after intravenous (IV) injection, respectively. While these contrast agents based on small molecules have been widely used or hold great potential in the clinics, one major limitation is that they are only suitable for single modality imaging. As a result, the strengths of different imaging techniques are hardly integrated together for better disease management. To address this challenge, significant efforts have been devoted to developing multimodal imaging probes in the past decades.[5] One general approach is to integrate different functional small molecules together using elegant synthetic strategies.[5d, 6] For example, Banerjee et al. reported a small-molecule-based dual modality SPECT/nearinfrared fluorescence (NIRF) imaging agent, which shows high and specific uptake in prostate-specific membrane antigen (PSMA) positive xenografts and excellent pharmacokinetics for targeting PSMA invivo.[5d] As a parallel direction, nanoparticle (NP) based multimodal imaging probes have also attracted great attention because inorganic NPs typically exhibit large surface/volume ratios, tunable and diverse material properties.[5e, 7] For instance, radioactive quantum dots (QDs) labelled with 64Cu have been used in fluorescence and PET imaging.[8] Lin et al. developed robust luminescent and paramagnetic hybrid silica NPs for optical and magnetic resonance imaging (MRI), respectively.[5a] Gold NPs (AuNPs) not only can serve as nonphotobleaching emitters in dark-field, Raman, and photothermal imaging in vitro,[9] but also can be used to enhance contrasts of photoacoustics and computed tomography imaging in vivo.[10] While these exciting biomedical applications are continuously driving the emergence of novel multimodal nanoprobes, inorganic NPs often exhibit pharmacokinetics different from those of small-molecule contrast agents. For instance, carbon nanotubes [11] and iron oxide NPs [12] only shown a short firstorder exponential blood circulation with half-lives of about 1.0 h and about 0.12 h after IV injection, respectively. In addition, reticuloendothelial system (RES) organs often rapidly sequester these nanostructures, resulting in slow RES clearance processes and potential health hazards.[7g, 9c, 13] These limitations in pharmacokinetics of NPs significantly hamper their clinical applications. Thus, it is highly desirable to develop nanoprobes that possess diverse material properties suitable for different imaging techniques and also exhibit optimal in vivo pharmacokinetics. The biodistribution, renal clearance, and pharmacokinetics of nanoprobes mainly depend on their particle sizes and surfaces.[14] For example, multifunctional silica-based particles smaller than 5nm can effectively evade uptake by the reticulo-endothelial system (RES).[14e] In addition to the …