Ueda Katsuya, Ma Chuang, Izumiya Makoto, Kuroda Chika, Ishida Haruka, Uemura Takeshi, Saito Naoto, Aoki Kaoru, Haniu Hisao
Biomedical Engineering Division, Graduate School of Medicine, Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Nagano, Japan.
Department of Organ Anatomy and Nanomedicine, Graduate School of Medicine, Yamaguchi University 1-1-1 Minami-Kogushi Ube, Yamaguchi 755-8505, Japan.
Nanomaterials (Basel). 2023 Jan 5;13(2):244. doi: 10.3390/nano13020244.
With the advent of nanotechnology, the use of nanoparticles as drug delivery system (DDS) has attracted great interest. We aimed to apply carbon nanohorns (CNHs) as DDS in the development of new treatments for bone diseases. We evaluated the in vitro and in vivo cellular responses of CNHs in bone-related cells compared with carbon blacks (CBs), which are similar in particle size but differ in surface and structural morphologies. Although in vitro experiments revealed that both CNHs and CBs were incorporated into the lysosomes of RAW264-induced osteoclast-like cells (OCs) and MC3T3-E1 osteoblast-like cells (OBs), no severe cytotoxicity was observed. CNHs reduced the tartrate-resistant acid phosphatase activity and expression of the differentiation marker genes in OCs at noncytotoxic concentrations, whereas the alkaline phosphatase activity and differentiation of OBs increased. Under calcification of OBs, CNHs increased the number of calcified nodules and were intra- and extracellularly incorporated into calcified vesicles to form crystal nuclei. The in vivo experiments showed significant promotion of bone regeneration in the CNH group alone, with localized CNHs being found in the bone matrix and lacunae. The suppression of OCs and promotion of OBs suggested that CNHs may be effective against bone diseases and could be applied as DDS.
随着纳米技术的出现,使用纳米颗粒作为药物递送系统(DDS)已引起了极大的关注。我们旨在将碳纳米角(CNHs)用作DDS,以开发治疗骨疾病的新方法。我们评估了与炭黑(CBs)相比,CNHs在骨相关细胞中的体外和体内细胞反应,CBs的粒径相似,但表面和结构形态不同。尽管体外实验表明,CNHs和CBs都被RAW264诱导的破骨细胞样细胞(OCs)和MC3T3-E1成骨细胞样细胞(OBs)的溶酶体摄取,但未观察到严重的细胞毒性。在无细胞毒性浓度下,CNHs降低了OCs中抗酒石酸酸性磷酸酶活性和分化标记基因的表达,而OBs的碱性磷酸酶活性和分化增加。在OBs钙化过程中,CNHs增加了钙化结节的数量,并在细胞内和细胞外被整合到钙化小泡中形成晶核。体内实验表明,仅CNH组的骨再生得到显著促进,在骨基质和腔隙中发现了局部的CNHs。对OCs的抑制和对OBs的促进表明,CNHs可能对骨疾病有效,并可作为DDS应用。