Li Hung-Cheng, Hsieh Feng-Jen, Chen Ching-Pin, Chang Ming-Yao, Hsieh Patrick C H, Chen Chia-Chun, Hung Shain-Un, Wu Che-Chih, Chang Huan-Cheng
1] Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan [2].
Sci Rep. 2013 Oct 25;3:3044. doi: 10.1038/srep03044.
Low-dimensional carbon-based nanomaterials have recently received enormous attention for biomedical applications. However, increasing evidence indicates that they are cytotoxic and can cause inflammatory responses in the body. Here, we show that monocrystalline nanodiamonds (NDs) synthesized by high-pressure-high-temperature (HPHT) methods and purified by air oxidation and strong oxidative acid treatments have excellent hemocompatibility with negligible hemolytic and thrombogenic activities. Cell viability assays with human primary endothelial cells suggested that the oxidized HPHT-NDs (dimensions of 35-500 nm) are non-cytotoxic. No significant elevation of the inflammatory cytokine levels of IL-1β and IL-6 was detected in mice after intravenous injection of the nanocrystals in vivo. Using a hindlimb-ischemia mouse model, we demonstrated that 35-nm NDs after covalent conjugation with polyarginine are useful as a drug delivery vehicle of heparin for prolonged anticoagulation treatment. The present study lays a solid foundation for further therapeutic applications of NDs in biomedicine.
低维碳基纳米材料近来在生物医学应用方面受到了极大关注。然而，越来越多的证据表明它们具有细胞毒性，并且会在体内引发炎症反应。在此，我们表明，通过高温高压（HPHT）方法合成、经空气氧化和强氧化酸处理纯化的单晶纳米金刚石（NDs）具有出色的血液相容性，溶血和血栓形成活性可忽略不计。用人原代内皮细胞进行的细胞活力测定表明，氧化后的HPHT-NDs（尺寸为35 - 500纳米）无细胞毒性。在小鼠体内静脉注射纳米晶体后，未检测到白细胞介素-1β和白细胞介素-6等炎症细胞因子水平有显著升高。利用后肢缺血小鼠模型，我们证明了与聚精氨酸共价结合后的35纳米NDs可作为肝素的药物递送载体用于延长抗凝治疗。本研究为NDs在生物医学中的进一步治疗应用奠定了坚实基础。
