Nanosafety Research Group, School of Life Sciences, Heriot-Watt University, Edinburgh, EH14 4AS,UK.
J Control Release. 2012 Dec 28;164(3):307-13. doi: 10.1016/j.jconrel.2012.08.018. Epub 2012 Aug 23.
Nanomaterials (NMs) have the potential to improve the treatment and diagnosis of disease as they are suitable candidates for a number of diagnostic and therapeutic applications. On entering the body via a variety of exposure routes, and during their translocation to secondary target sites it is inevitable that NMs interact with biological molecules, such as proteins. These interactions may influence the behaviour and toxicity of NMs following exposure. As the surface of NMs is what interacts with cells and tissues it is necessary to identify the influence of NM surface properties on their toxicity, and determine how this is influenced by the route of exposure, and physico-chemical characteristics of NMs. The term protein corona is used to describe the coating of the NM surface with protein. The protein corona is a dynamic and complex structure whose composition is dictated by the biological medium and the physico-chemical properties of NMs (such as their size, composition, hydrophobicity and charge) as this influences protein binding specificity and affinity. Depending on the route of exposure (e.g. inhalation or injection) NMs will encounter different proteins. We have observed that i) the composition of protein corona of NMs is likely to be dictated by their route of entry, ii) the translocation of NMs to secondary target sites may influence the composition of the protein corona (i.e. they encounter different proteins on their transport in the body) so that the composition of the protein corona evolves over time, iii) the physico-chemical characteristics of NMs dictate the composition of the protein corona, and the toxicity of NMs and iv) NMs can affect secondary target sites that vary according to delivery route and corona composition following exposure. These findings, and evidence from the wider literature has therefore led us to hypothesise that NM toxicity is dictated by the exposure route due to the acquisition of a surface coating (protein corona) that is determined by the route of entry and physico-chemical properties of the NM. This information can be exploited within the intelligent design of NMs in the future (e.g. to control protein adsorption and the subsequent cellular response), and be used to improve the design of toxicology investigations (e.g. to inform how NMs should be dispersed within in vitro experiments to more accurately reflect in vivo conditions).
纳米材料（NMs）具有改善疾病治疗和诊断的潜力，因为它们是许多诊断和治疗应用的合适候选材料。NMs 通过多种暴露途径进入体内，并在转移到次级靶位的过程中，不可避免地与生物分子（如蛋白质）相互作用。这些相互作用可能会影响暴露后 NMs 的行为和毒性。由于 NMs 的表面与细胞和组织相互作用，因此有必要确定 NM 表面特性对其毒性的影响，并确定这种影响如何受到暴露途径和 NMs 的物理化学特性的影响。术语“蛋白质冠”用于描述 NM 表面的蛋白质涂层。蛋白质冠是一种动态而复杂的结构，其组成由生物介质和 NMs 的物理化学特性（如大小、组成、疏水性和电荷）决定，因为这会影响蛋白质结合的特异性和亲和力。根据暴露途径（例如吸入或注射），NMs 将遇到不同的蛋白质。我们已经观察到：i）NM 蛋白质冠的组成可能由其进入途径决定，ii）NM 向次级靶位的转移可能会影响蛋白质冠的组成（即它们在体内运输过程中遇到不同的蛋白质），因此蛋白质冠的组成随时间演变，iii）NMs 的物理化学特性决定了蛋白质冠的组成以及 NMs 的毒性，iv）NMs 可以影响根据暴露后的输送途径和冠组成而变化的次级靶位。这些发现以及更广泛的文献证据使我们假设，由于 NM 获得了由进入途径和 NM 的物理化学特性决定的表面涂层（蛋白质冠），因此 NM 毒性由暴露途径决定。未来可以利用这些信息对 NMs 进行智能设计（例如，控制蛋白质吸附和随后的细胞反应），并用于改进毒理学研究的设计（例如，告知如何在体外实验中分散 NMs，以更准确地反映体内条件）。
