Hua Changxing, Lu Zeyi, Cui Wenjing, Ren Wei, Xu Yi, Li Jinglin, Zhao Xudong, Zhao Shiyong, Kang Pengcheng, Cui Yunfu
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China.
Postgraduate Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China.
Mikrochim Acta. 2026 Jan 26;193(2):110. doi: 10.1007/s00604-025-07759-w.
Hepatocellular carcinoma (HCC), accounting for 75-85% of liver cancers, faces limited therapeutic efficacy due to late-stage diagnosis, high malignancy, and poor drug permeability. Sorafenib (SF), a first-line multi-kinase inhibitor for unresectable HCC, suffers from low tumor-targeting efficiency and adverse effects. This study proposes a urease-driven nanomotor system (CUNMs + SF) to enhance SF delivery and tumor penetration. The nanomotors utilize porous magnetic silica nanoparticles (PMSNs) loaded with SF and modified with cyclodextrin-urease hybrids. This design enables magnetic targeting to HCC sites and autonomous propulsion via urea-fueled enzymatic conversion, overcoming physiological barriers in the tumor microenvironment.The system exhibits pH-responsive drug release (triggered at pH < 6.5) and induces ferroptosis in HCC cells by inhibiting the SLC7A13/GSH/GPX4 pathway, effectively suppressing tumor growth. In vitro and in vivo experiments demonstrate superior tumor accumulation, deep tissue penetration, and enhanced therapeutic outcomes compared to conventional SF. This work pioneers the application of enzyme-powered nanomotors in HCC therapy, addressing the limitations of systemic drug delivery while leveraging tumor-specific biochemical cues. The findings highlight the potential of biohybrid nanomotors for targeted cancer treatment and inspire future developments in stimuli-responsive nanomedicine for challenging malignancies.
