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Urease-driven nanomotors loaded with sorafenib for magnetically-guided accumulation and deep tissue penetration towards hepatocellular carcinoma therapy via ferroptosis induction.

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Title: Urease-driven nanomotors loaded with sorafenib for magnetically-guided accumulation and deep tissue penetration towards hepatocellular carcinoma therapy via ferroptosis induction.
Authors: Hua C; Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China., Lu Z; Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China., Cui W; Postgraduate Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China., Ren W; The second Department of General Surgery, Second Hospital of Harbin, Harbin, Heilongjiang, 150056, China., Xu Y; Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China., Li J; Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China., Zhao X; Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China., Zhao S; Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China., Kang P; Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China. kang_pengcheng@126.com., Cui Y; Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China. yfcui7@163.com.
Source: Mikrochimica acta [Mikrochim Acta] 2026 Jan 26; Vol. 193 (2), pp. 110. Date of Electronic Publication: 2026 Jan 26.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Springer-Verlag Country of Publication: Austria NLM ID: 7808782 Publication Model: Electronic Cited Medium: Internet ISSN: 1436-5073 (Electronic) Linking ISSN: 00263672 NLM ISO Abbreviation: Mikrochim Acta Subsets: MEDLINE
Imprint Name(s): Original Publication: Wien ; New York : Springer-Verlag.
MeSH Terms: Sorafenib*/pharmacology , Sorafenib*/chemistry , Sorafenib*/therapeutic use , Sorafenib*/metabolism , Liver Neoplasms*/drug therapy , Liver Neoplasms*/pathology , Liver Neoplasms*/metabolism , Carcinoma, Hepatocellular*/drug therapy , Carcinoma, Hepatocellular*/pathology , Carcinoma, Hepatocellular*/metabolism , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry , Antineoplastic Agents*/therapeutic use , Urease*/metabolism , Urease*/chemistry , Ferroptosis*/drug effects, Silicon Dioxide/chemistry ; Drug Carriers/chemistry ; Magnetite Nanoparticles/chemistry ; Humans ; Animals ; Mice ; Drug Liberation ; Cell Line, Tumor
Abstract: 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.
(© 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
Competing Interests: Declarations. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests.
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Grant Information: Y-QL202201-0020 Beijing Xisike Clinical Oncology Research Foundation
Contributed Indexing: Keywords: Ferroptosis; Hepatocellular carcinoma; Magnetic silica nanoparticles; Nanomotors; Sorafenib; Urease
Substance Nomenclature: 9ZOQ3TZI87 (Sorafenib)
0 (Antineoplastic Agents)
EC 3.5.1.5 (Urease)
7631-86-9 (Silicon Dioxide)
0 (Drug Carriers)
0 (Magnetite Nanoparticles)
Entry Date(s): Date Created: 20260126 Date Completed: 20260701 Latest Revision: 20260701
Update Code: 20260701
DOI: 10.1007/s00604-025-07759-w
PMID: 41586895
Database: MEDLINE
Description
ISSN:1436-5073
DOI:10.1007/s00604-025-07759-w