Schanen Brian C, Karakoti Ajay S, Seal Sudipta, Drake Donald R, Warren William L, Self William T
VaxDesign Corporation, 12612 Challenger Parkway, Suite 365, Orlando, Florida 32826, USA.
ACS Nano. 2009 Sep 22;3(9):2523-32. doi: 10.1021/nn900403h.
Nanoparticle technology is undergoing significant expansion largely because of the potential of nanoparticles as biomaterials, drug delivery vehicles, cancer therapeutics, and immunopotentiators. Incorporation of nanoparticle technologies for in vivo applications increases the urgency to characterize nanomaterial immunogenicity. This study explores titanium dioxide, one of the most widely manufactured nanomaterials, synthesized into its three most common nanoarchitectures: anatase (7-10 nm), rutile (15-20 nm), and nanotube (10-15 nm diameters, 70-150 nm length). The fully human autologous MIMIC immunological construct has been utilized as a predictive, nonanimal alternative to diagnose nanoparticle immunogenicity. Cumulatively, treatment with titanium dioxide nanoparticles in the MIMIC system led to elevated levels of proinflammatory cytokines and increased maturation and expression of costimulatory molecules on dendritic cells. Additionally, these treatments effectively primed activation and proliferation of naive CD4(+) T cells in comparison to dendritic cells treated with micrometer-sized (>1 microm) titanium dioxide, characteristic of an in vivo inflammatory response.
纳米颗粒技术正在经历显著的发展，这主要是因为纳米颗粒作为生物材料、药物递送载体、癌症治疗剂和免疫增强剂的潜力。将纳米颗粒技术应用于体内增加了表征纳米材料免疫原性的紧迫性。本研究探索了二氧化钛，这是制造最为广泛的纳米材料之一，将其合成三种最常见的纳米结构：锐钛矿型（7 - 10纳米）、金红石型（15 - 20纳米）和纳米管（直径10 - 15纳米，长度70 - 150纳米）。完全人源自体的MIMIC免疫构建体已被用作一种预测性的、非动物替代方法来诊断纳米颗粒的免疫原性。总体而言，在MIMIC系统中用二氧化钛纳米颗粒处理导致促炎细胞因子水平升高，树突状细胞上共刺激分子的成熟和表达增加。此外，与用微米级（>1微米）二氧化钛处理的树突状细胞相比，这些处理有效地启动了初始CD4(+) T细胞的活化和增殖，这是体内炎症反应的特征。
