Wang Zhi-Hao, Zeng Xuejiao, Zhang Shuhao, Li Hailong, Zhou Jianchao, Yang Yefei, Huang Wanting, Zhao Fengqin, Liu Zhongyang, Liu Junjie, Hu Yurong, Shi Jinjin
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Henan Key Laboratory of Nanomedicine for Targeting Diagnosis and Treatment, Zhengzhou 450001, China.
ACS Nano. 2025 May 13;19(18):17228-17246. doi: 10.1021/acsnano.4c07866. Epub 2025 Apr 29.
Oral administration is a traditional, safe, and widely used drug delivery strategy. However, the delivery efficiency of the oral drug delivery system is hindered by the long gastrointestinal tract, filled with dense and viscous mucus. Herein, we presented an acoustic-magnetic responsive nanomotor (MMSNP) for oral drug delivery via gastrointestinal site navigation and mucus layer penetration. MMSNP has a Janus rod-shaped structure composed of iron tetroxide and mesoporous silica, which could be guided to various intestinal segments with an external magnetic field based on the demand of different diseases. In addition, the rod-like system could effectively penetrate the dense and viscous mucus under ultrasound radiation to improve the bioavailability of loaded drugs. In diabetes rats, small intestinal navigation and mucus penetration of the nanomotor increased the oral relative bioavailability of metformin (Met) by 78.0% and the effective hypoglycemic time by 1.1-fold than pure Met. In orthotopic colorectal cancer (CRC)-bearing mice, magnetically mediated colorectal navigation increased the anchoring efficiency of nanomotors by 4.2-fold, and ultrasound propulsion increased the mucus penetration efficiency of MMSNP by 5.2-fold, leading to a vastly improved delivery efficiency of cisplatin (CP) and a superior tumor inhibition rate of 97.2%. This simple and versatile nanomotor has broad application prospects in the treatment of gastrointestinal diseases, providing a promising and universal strategy for clinical conversion of orally administered drugs.
口服给药是一种传统、安全且广泛应用的药物递送策略。然而，口服给药系统的递送效率受到充满致密且粘稠黏液的长胃肠道的阻碍。在此，我们展示了一种用于口服给药的声磁响应纳米马达（MMSNP），其可通过胃肠道部位导航和黏液层穿透实现药物递送。MMSNP具有由四氧化三铁和介孔二氧化硅组成的 Janus 棒状结构，基于不同疾病的需求，其可在外加磁场引导下到达各个肠段。此外，棒状系统在超声辐射下可有效穿透致密且粘稠的黏液，以提高所载药物的生物利用度。在糖尿病大鼠中，纳米马达的小肠导航和黏液穿透能力使二甲双胍（Met）的口服相对生物利用度提高了78.0%，有效降糖时间比单纯Met延长了1.1倍。在原位结直肠癌（CRC）荷瘤小鼠中，磁介导的结肠导航使纳米马达的锚定效率提高了4.2倍，超声推进使MMSNP的黏液穿透效率提高了5.2倍，从而极大地提高了顺铂（CP）的递送效率，并产生了97.2%的优异肿瘤抑制率。这种简单且多功能的纳米马达在胃肠道疾病治疗中具有广阔的应用前景，为口服药物的临床转化提供了一种有前景且通用的策略。
