Rong Rui, Zhang Yun, Tan Weihang, Hu Tingting, Wang Xiaoqin, Gui Zongxiang, Gong Jiachun, Xu Xiaolong
Department of Chemistry, University of Science and Technology of China, Hefei, 230026, PR China.
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China.
ACS Appl Bio Mater. 2020 Nov 16;3(11):7919-7929. doi: 10.1021/acsabm.0c01038. Epub 2020 Oct 21.
Nanomaterials have been widely applied in oral drug delivery. A number of indirect evidences suggest that nanoparticles can pass across gastrointestinal walls to enter the blood circulation system. However, there is still no direct evidence to prove that the intact nanoparticles can pass across gastrointestinal walls and the nanoparticles can retain their original structure after translocation across gastrointestinal walls. In the present study, the potential toxicity of dimercaptosuccinic acid coated Zn doped magnetite nanoparticles (DMSA-ZnFeO) in the spleen, stomach, and small intestine of mice has been investigated after 30 days of repeated intragastric administration. We provide first direct evidence that intact DMSA-ZnFeO can pass across the small intestinal barriers to enter blood circulation system and arrive in the spleen. In addition, our findings provide direct evidence that although the biotransformation of DMSA-ZnFeO occurs in vivo, some DMSA-ZnFeO retain their original structure after translocation across the small intestinal wall and deposition in the spleen. The results indicate the safety of DMSA-ZnFeO in the applications in mice at a 50 mg/kg dose and highlight the unique advantage of DMSA-ZnFeO in biomedical applications.
纳米材料已广泛应用于口服药物递送。许多间接证据表明,纳米颗粒可穿过胃肠道壁进入血液循环系统。然而,仍没有直接证据证明完整的纳米颗粒能够穿过胃肠道壁,以及纳米颗粒在穿过胃肠道壁后仍能保持其原始结构。在本研究中,对经30天重复灌胃给药后二巯基丁二酸包覆的锌掺杂磁铁矿纳米颗粒(DMSA-ZnFeO)在小鼠脾脏、胃和小肠中的潜在毒性进行了研究。我们首次提供了直接证据,证明完整的DMSA-ZnFeO能够穿过小肠屏障进入血液循环系统并到达脾脏。此外,我们的研究结果提供了直接证据,表明尽管DMSA-ZnFeO在体内发生了生物转化,但一些DMSA-ZnFeO在穿过小肠壁并沉积在脾脏后仍保持其原始结构。结果表明,50mg/kg剂量的DMSA-ZnFeO在小鼠体内应用是安全的,并突出了DMSA-ZnFeO在生物医学应用中的独特优势。