Nanoparticles for imaging: top or flop?
Nanoparticles for imaging: top or flop?
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DOI：
10.1148/radiol.14131520
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发表时间：
2014-10
期刊：
影响因子：
19.7
通讯作者：
Lammers T
中科院分区：
文献类型：
--
作者：
Kiessling F;Mertens ME;Grimm J;Lammers T
纳米颗粒经常被建议作为诊断剂。然而，除了氧化铁纳米颗粒，迄今为止诊断纳米颗粒几乎没有被纳入临床使用。这主要是由于难以实现可接受的药代动力学性质和可重现的颗粒均匀性以及对毒性、生物降解和消除的担忧。纳米粒的合理临床应用指征应考虑其生物学行为。例如，许多纳米颗粒被巨噬细胞吸收并积聚在富含巨噬细胞的组织中。因此，它们可用于在肝脏、脾脏、淋巴结和炎性病变（如动脉粥样硬化斑块）中提供对比。此外，细胞可以有效地用纳米颗粒标记，使植入（干）细胞和组织工程移植物的定位以及细胞的体内迁移研究成为可能。使用纳米颗粒进行分子成像的潜力受到损害，因为它们的药代动力学特性难以控制。纳米颗粒的理想靶点位于内皮管腔表面上，而靶向纳米颗粒递送至血管外结构通常是有限的，并且难以与潜在的增强渗透性和保留（EPR）效应分开。大多数临床上使用的基于纳米颗粒的药物递送系统是基于EPR效应，并且对于其更个性化的使用，可以并入成像标记物以监测生物分布、靶位点积累、药物释放和治疗功效。总之，尽管纳米颗粒并不总是分子成像的正确选择（因为更小或更大的分子可能提供更具体的信息），但纳米颗粒在其他诊断和治疗诊断应用中具有巨大的临床潜力。
Nanoparticles are frequently suggested as diagnostic agents. However, except for iron oxide nanoparticles, diagnostic nanoparticles have been barely incorporated into clinical use so far. This is predominantly due to difficulties in achieving acceptable pharmacokinetic properties and reproducible particle uniformity as well as to concerns about toxicity, biodegradation, and elimination. Reasonable indications for the clinical utilization of nanoparticles should consider their biologic behavior. For example, many nanoparticles are taken up by macrophages and accumulate in macrophage-rich tissues. Thus, they can be used to provide contrast in liver, spleen, lymph nodes, and inflammatory lesions (eg, atherosclerotic plaques). Furthermore, cells can be efficiently labeled with nanoparticles, enabling the localization of implanted (stem) cells and tissue-engineered grafts as well as in vivo migration studies of cells. The potential of using nanoparticles for molecular imaging is compromised because their pharmacokinetic properties are difficult to control. Ideal targets for nanoparticles are localized on the endothelial luminal surface, whereas targeted nanoparticle delivery to extravascular structures is often limited and difficult to separate from an underlying enhanced permeability and retention (EPR) effect. The majority of clinically used nanoparticle-based drug delivery systems are based on the EPR effect, and, for their more personalized use, imaging markers can be incorporated to monitor biodistribution, target site accumulation, drug release, and treatment efficacy. In conclusion, although nanoparticles are not always the right choice for molecular imaging (because smaller or larger molecules might provide more specific information), there are other diagnostic and theranostic applications for which nanoparticles hold substantial clinical potential.
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