Lipase-powered asymmetric silica nanomotors with a tailored head-tail structure for enhanced mucus penetration

Mucus is a major barrier that impedes the effective delivery of orally administered drugs. In this study, we have developed a series of silica nanomotors with adjustable head tail structures and lipase modification. The impact of the lipase distribution on the movement velocity and penetration efficiency of the nanomotors within the mucus layer was investigated in vitro and in vivo. Our results show that lipase-powered asymmetric silica nanomotors with a short tail (Lipase-AMSN-S) can effectively penetrate through the mucus and epithelial barriers, which possibly attributed to its easy enzyme-substrate accessibility and asymmetric lipase distribution. These findings offer a promising strategy for enhancing oral drug delivery efficiency.