IRCCS- Istituto di Ricerche Farmacologiche Mario , Negri, Milan, 20156, Italy.
Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin , Dublin, Dublin 4, Ireland.
ACS Nano. 2017 Jun 27;11(6):5519-5529. doi: 10.1021/acsnano.7b00497. Epub 2017 Jun 6.
The transport and the delivery of drugs through nanocarriers is a great challenge of pharmacology. Since the production of liposomes to reduce the toxicity of doxorubicin in patients, a plethora of nanomaterials have been produced and characterized. Although it is widely known that elementary properties of nanomaterials influence their in vivo kinetics, such interaction is often poorly investigated in many preclinical studies. The present study aims to evaluate the actual effect of size and shape on the biodistribution of a set of gold nanoparticles (GNPs) after intravenous administration in mice. To this goal, quantitative data achieved by inductively coupled plasma mass spectrometry and observational results emerging from histochemistry (autometallography and enhanced dark-field hyperspectral microscopy) were combined. Since the immune system plays a role in bionano-interaction we used healthy immune-competent mice. To keep the immune surveillance on the physiological levels we synthesized endotoxin-free GNPs to be tested in specific pathogen-free animals. Our study mainly reveals that (a) the size and the shape greatly influence the kinetics of accumulation and excretion of GNPs in filter organs; (b) spherical and star-like GNPs showed the same percentage of accumulation, but a different localization in liver; (c) only star-like GNPs are able to accumulate in lung; (d) changes in the geometry did not improve the passage of the blood brain barrier. Overall, this study can be considered as a reliable starting point to drive the synthesis and the functionalization of potential candidates for theranostic purposes in many fields of research.
纳米载体介导的药物输送是药理学的一大挑战。自从生产脂质体来降低多柔比星在患者中的毒性以来，已经生产出了大量的纳米材料并对其进行了表征。尽管人们普遍知道纳米材料的基本性质会影响其体内动力学，但在许多临床前研究中，这种相互作用往往没有得到很好的研究。本研究旨在评估一系列金纳米颗粒（GNPs）在静脉给药后，大小和形状对其体内分布的实际影响。为此，我们将电感耦合等离子体质谱法获得的定量数据与组织化学（自动金属成像和增强暗场高光谱显微镜）得出的观察结果相结合。由于免疫系统在生物纳米相互作用中发挥作用，我们使用了健康的免疫功能正常的小鼠。为了保持免疫监测处于生理水平，我们合成了无内毒素的 GNPs，以便在特定无病原体动物中进行测试。我们的研究主要揭示了：（a）大小和形状极大地影响了 GNPs 在过滤器官中的积累和排泄动力学；（b）球形和星形 GNPs 具有相同的积累百分比，但在肝脏中的定位不同；（c）只有星形 GNPs 能够在肺部积累；（d）几何形状的变化并没有改善血脑屏障的通透性。总的来说，这项研究可以被认为是一个可靠的起点，为治疗目的的候选物的合成和功能化提供了指导，在许多研究领域都有应用前景。
