Acoustic-Magnetic Responsive Nanomotor Augments Oral Drug Delivery by Gastrointestinal Site Navigation and Mucus Layer Penetration

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.