Shi Yujie, Shi Zujin, Li Suxin, Zhang Yuan, He Bing, Peng Dong, Tian Jie, Zhao Ming, Wang Xueqing, Zhang Qiang
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences.
Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing, People's Republic of China.
Int J Nanomedicine. 2017 Jun 1;12:4177-4194. doi: 10.2147/IJN.S133295. eCollection 2017.
Single-wall carbon nanohorns (SWCNHs), which have multitudes of horn interstices, an extensive surface area, and a spherical aggregate structure, offer many advantages over other carbon nanomaterials being used as a drug nanovector. The previous studies on the interaction between SWCNHs and cells have mostly emphasized on cellular uptake and intracellular trafficking, but seldom on epithelial cells. Polar epithelium as a typical biological barrier constitutes the prime obstacle for the transport of therapeutic agents to target site. This work tried to explore the permeability of SWCNHs through polar epithelium and their abilities to modulate transcellular transport, and evaluate the potential of SWCNHs in drug delivery. Madin-Darby canine kidney (MDCK) cell monolayer was used as a polar epithelial cell model, and as-grown SWCNHs, together with oxidized and fluorescein isothiocyanate-conjugated bovine serum albumin-labeled forms, were constructed and comprehensively investigated in vitro and in vivo. Various methods such as transmission electron microscopy and confocal imaging were used to visualize their intracellular uptake and localization, as well as to investigate the potential transcytotic process. The related mechanism was explored by specific inhibitors. Additionally, fast multispectral optoacoustic tomography imaging was used for monitoring the distribution and transport process of SWCNHs in vivo after oral administration in nude mice, as an evidence for their interaction with the intestinal epithelium. The results showed that SWCNHs had a strong bioadhesion property, and parts of them could be uptaken and transcytosed across the MDCK monolayer. Multiple mechanisms were involved in the uptake and transcytosis of SWCNHs with varying degrees. After oral administration, oxidized SWCNHs were distributed in the gastrointestinal tract and retained in the intestine for up to 36 h probably due to their surface adhesion and endocytosis into the intestinal epithelium. Overall, this comprehensive investigation demonstrated that SWCNHs can serve as a promising nanovector that can cross the barrier of polar epithelial cells and deliver drugs effectively.
单壁碳纳米角（SWCNHs）具有众多的角间隙、较大的表面积和球形聚集体结构，与用作药物纳米载体的其他碳纳米材料相比具有许多优势。先前关于SWCNHs与细胞相互作用的研究大多侧重于细胞摄取和细胞内运输，但很少涉及上皮细胞。极性上皮作为一种典型的生物屏障，是治疗药物运输到靶部位的主要障碍。这项工作试图探索SWCNHs通过极性上皮的渗透性及其调节跨细胞运输的能力，并评估SWCNHs在药物递送中的潜力。使用Madin-Darby犬肾（MDCK）细胞单层作为极性上皮细胞模型，构建了生长态的SWCNHs以及氧化型和异硫氰酸荧光素偶联的牛血清白蛋白标记形式，并在体外和体内进行了全面研究。使用透射电子显微镜和共聚焦成像等各种方法来观察它们的细胞内摄取和定位，以及研究潜在的转胞吞过程。通过特异性抑制剂探索相关机制。此外，快速多光谱光声断层成像用于监测裸鼠口服给药后SWCNHs在体内的分布和运输过程，作为它们与肠上皮相互作用的证据。结果表明，SWCNHs具有很强的生物粘附特性，其中部分可以被摄取并跨MDCK单层进行转胞吞。SWCNHs的摄取和转胞吞涉及多种程度不同的机制。口服给药后，氧化型SWCNHs分布在胃肠道并在肠道中保留长达36小时，这可能是由于它们的表面粘附和被肠上皮细胞内吞。总体而言，这项全面研究表明，SWCNHs可以作为一种有前途的纳米载体，能够跨越极性上皮细胞屏障并有效地递送药物。
