Biocompatibility Assessment of Detonation Nanodiamond in Non-Human Primates and Rats Using Histological, Hematologic, and Urine Analysis
Biocompatibility Assessment of Detonation Nanodiamond in Non-Human Primates and Rats Using Histological, Hematologic, and Urine Analysis
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DOI：
10.1021/acsnano.6b00839
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发表时间：
2016-08-01
期刊：
影响因子：
17.1
通讯作者：
Ho, Dean
中科院分区：
文献类型：
--
作者：
Moore, Laura;Yang, Junyu;Ho, Dean
爆轰纳米金刚石（DND）由于具有多种有前途的性质，已被广泛探索用于从癌症治疗到磁共振成像的生物医学应用。这些包括多面表面，其介导有效的药物结合和水协调，从而显著增强药物递送和成像的功效和安全性。此外，DND的可扩展处理产生均匀的颗粒。此外，广泛的生物相容性研究表明，DND似乎耐受良好。在将DND用于通过静脉给药解决的适应症的临床转化之前，需要在小型和大型动物临床前模型中全面评估DND的安全性。本文报告了在非人灵长类动物和大鼠中进行DND生物相容性研究的结果。大鼠研究是在两个队列中进行的多次给药亚急性研究，持续2周，包括组织学、血清和尿液分析。非人灵长类动物研究是在标准/临床相关和升高剂量队列中进行的双性别、多次给药和长期研究，持续6个月，包括全面的血清、尿液、组织学和体重分析。这些研究的结果表明，ND在临床相关剂量下耐受良好。生物标志物水平的剂量依赖性变化的检查为DND用于临床药物递送和成像的下游人体验证提供了重要指导。
Detonation nanodiamonds (DNDs) have been widely explored for biomedical applications ranging from cancer therapy to magnetic resonance imaging due to several promising properties. These include faceted surfaces that mediate potent drug binding and water coordination that have resulted in marked enhancements to the efficacy and safety of drug delivery and imaging. In addition, scalable processing of DNDs yields uniform particles. Furthermore, a broad spectrum of biocompatibility studies has shown that DNDs appear to be well-tolerated. Prior to the clinical translation of DNDs for indications that are addressed via intravenous administration, comprehensive assessment of DND safety in both small and large animal preclinical models is needed. This article reports the results of a DND biocompatibility study in both non-human primates and rats. The rat study was performed as a multiple dose subacute investigation in two cohorts that lasted for 2 weeks and included histological, serum, and urine analysis. The non-human primate study was performed as a dual gender, multiple dose, and long-term investigation in both standard/clinically relevant and elevated dosing cohorts that lasted for 6 months and included comprehensive serum, urine, histological, and body weight analysis. The results from these studies indicate that NDs are well-tolerated at clinically relevant doses. Examination of dose-dependent changes in biomarker levels provides important guidance for the downstream in-human validation of DNDs for clinical drug delivery and imaging.