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首页> 外文期刊>RSC Advances >Impact of soft protein interactions on the excretion, extent of receptor occupancy and tumor accumulation of ultrasmall metal nanoparticles: a compartmental model simulation
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Impact of soft protein interactions on the excretion, extent of receptor occupancy and tumor accumulation of ultrasmall metal nanoparticles: a compartmental model simulation

机译：软蛋白相互作用对超小金属纳米颗粒的排泄，受体占有程度和肿瘤积累的影响：隔室模型模拟

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Ultrasmall metal nanoparticles (NPs) are next-generation nano-based platforms for in vivo disease diagnosis and treatment. Due to their small size below the kidney filtration threshold and marked resistance to nonspecific serum protein adsorption, ultrasmall NPs can be rapidly excreted through the kidneys and escape liver uptake. However, although ultrasmall particles may be deemed highly resistant to protein adsorption, the real extent of this resistance is not known. Here, a simple compartmental model simulation was therefore implemented to understand how NP behavior in vivo could be modulated by soft, transient NP–plasma protein interactions characterized by dissociation constants in the millimolar range. In Model 1, ultrasmall NPs functionalized with a targeting probe, plasma proteins and target receptors were assumed to co-exist within a single compartment. Simulations were performed to understand the synergistic effect of soft interactions, systemic clearance and NP size on receptor occupancy in the single compartment. The results revealed the existence of a narrow range of ultraweak affinities and optimal particle sizes leading to greater target occupancy. In Model 2, simulations were performed to understand the impact of soft interactions on NP accumulation into a peripheral (tumor) compartment. The results revealed that soft interactions – but not active targeting – enhanced tumor uptake levels when tumor accumulation was limited by ‘fast’ plasma clearance and ‘slow’ vascular extravasation. The simple model presented here provides a basic framework to quantitatively understand the blood and tumor pharmacokinetics of ultrasmall NPs under the influence of transient protein interactions.
机译：超小金属纳米颗粒（NPs）是用于体内疾病诊断和治疗的下一代基于纳米的平台。由于它们的体积小至低于肾脏过滤阈值，并且对非特异性血清蛋白吸附具有显着的抵抗力，因此超小NP可以通过肾脏迅速排泄并逃脱肝脏吸收。但是，尽管可以认为超小颗粒对蛋白质的吸附具有很高的抵抗力，但这种抵抗力的真正程度尚不清楚。因此，这里进行了一个简单的区室模型模拟，以了解如何通过以毫摩尔范围内的解离常数为特征的，短暂的NP-血浆蛋白相互作用来调节体内的NP行为。在模型1中，假定使用靶向探针，血浆蛋白和靶受体功能化的超小型NP共存于单个隔室内。进行模拟以了解软相互作用，全身清除率和NP大小对单腔受体占用的协同作用。结果表明存在超弱亲和力和最佳粒径的窄范围存在，从而导致更大的目标占有率。在模型2中，进行了模拟以了解软相互作用对NP累积进入周围（肿瘤）腔室的影响。结果显示，当“快速”血浆清除率和“缓慢”血管外渗限制肿瘤积累时，软相互作用（而非主动靶向）可提高肿瘤吸收水平。这里介绍的简单模型提供了一个基本框架，可以定量了解在瞬时蛋白质相互作用的影响下超小型NP的血液和肿瘤药代动力学。

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