Fast and Autonomous Mannosylated Nanomotors for Dynamic Cancer Cell Targeting

Y Yuechi Liu (Bio‐Organic Chemistry Institute of Complex Molecular Systems Eindhoven University of Technology Helix, P. O. Box 513 Eindhoven 5600 MB the Netherlands) R Roberto Terracciano (Department of Chemistry University of Warwick Coventry CV4 7AL UK) J Jari Scheerstra (Bio‐Organic Chemistry Departments of Biomedical Engineering and Chemical Engineering & Chemistry Institute for Complex Molecular Systems Eindhoven University of Technology Eindhoven the Netherlands) G Gokhan Yilmaz (Department of Chemistry) H Hanglong Wu P Pascal Welzen (Bio‐Organic Chemistry Institute of Complex Molecular Systems Eindhoven University of Technology Helix, P. O. Box 513 Eindhoven 5600 MB the Netherlands) S Shoupeng Cao (College of Polymer Science and Engineering, National Key Laboratory of Advanced Polymer Materials) T Tania Patiño Padial (Bio-Organic Chemistry, Departments of Biomedical Engineering and Chemical Engineering & Chemistry, Institute for Complex Molecular Systems) L Loai Abdelmohsen (Department of Biomedical Engineering and Chemical Engineering and Chemistry Institute for Complex Molecular Systems Eindhoven University of Technology Helix, P. O. Box 513 Eindhoven 5600 MB The Netherlands) J Jingxin Shao (Bio-Organic Chemistry, Institute for Complex Molecular Systems (ICMS)) B Bingbing Sun (Bio-Organic Chemistry, Departments of Biomedical Engineering and Chemical Engineering & Chemistry, Institute for Complex Molecular Systems) C C. Remzi Becer (Department of Chemistry) J Jan C. M. van Hest (Bio-Organic Chemistry, Departments of Biomedical Engineering and Chemical Engineering and Chemistry, Institute for Complex Molecular Systems)

Abstract

AbstractAn attractive strategy in cancer cell therapy is to employ motile nanoparticles that can actively search for their target. Herein, we introduce mannosylated compartmentalized cross‐linked enzyme‐driven nanomotors (c‐CLEnM), which exhibit specific and efficient targeting of Hep G2 cells through elevated autonomous motion. In this design, we constructed biodegradable bowl‐shaped stomatocytes encapsulating the enzymes glucose oxidase (GOx) and catalase (CAT) within their nanocavity. A subsequent enzyme crosslinking reaction was performed to guarantee their stability. Furthermore, the c‐CLEnM were surface modified with a mannose‐functional glycopolymer, enabling binding with receptors expressed on Hep G2 cells. Interestingly, the targeting ligands on the nanomotors not only improved their specificity toward cancer cells but also enhanced motility. Compared to the non‐mannosylated nanomotors, mannosylated c‐CLEnM exhibited enhanced motion and higher targeting efficiency to cells in glucose‐containing ionic environments. The unexpected acceleration in speed resulted from the surface modification of these nanomotors with a glycopolymer layer, which increased the zeta potential and created a shielding effect that mitigated the influence of the surrounding ions. This nanomotor design highlights the synergistic effect of functional glycopolymer modification on cellular uptake, adding an additional level of control to nanomotors for application in cancer therapy.

Article Details

Volume / Issue Vol. 64, Issue 23
Published June 02, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (13)

Y

Yuechi Liu

Bio‐Organic Chemistry Institute of Complex Molecular Systems Eindhoven University of Technology Helix, P. O. Box 513 Eindhoven 5600 MB the Netherlands

R

Roberto Terracciano

Department of Chemistry University of Warwick Coventry CV4 7AL UK

J

Jari Scheerstra

Bio‐Organic Chemistry Departments of Biomedical Engineering and Chemical Engineering & Chemistry Institute for Complex Molecular Systems Eindhoven University of Technology Eindhoven the Netherlands

G

Gokhan Yilmaz

Department of Chemistry

H

Hanglong Wu

P

Pascal Welzen

Bio‐Organic Chemistry Institute of Complex Molecular Systems Eindhoven University of Technology Helix, P. O. Box 513 Eindhoven 5600 MB the Netherlands

S

Shoupeng Cao

College of Polymer Science and Engineering, National Key Laboratory of Advanced Polymer Materials

T

Tania Patiño Padial

Bio-Organic Chemistry, Departments of Biomedical Engineering and Chemical Engineering & Chemistry, Institute for Complex Molecular Systems

L

Loai Abdelmohsen

Department of Biomedical Engineering and Chemical Engineering and Chemistry Institute for Complex Molecular Systems Eindhoven University of Technology Helix, P. O. Box 513 Eindhoven 5600 MB The Netherlands

J

Jingxin Shao

Bio-Organic Chemistry, Institute for Complex Molecular Systems (ICMS)

B

Bingbing Sun

Bio-Organic Chemistry, Departments of Biomedical Engineering and Chemical Engineering & Chemistry, Institute for Complex Molecular Systems

C

C. Remzi Becer

Department of Chemistry

J

Jan C. M. van Hest

Bio-Organic Chemistry, Departments of Biomedical Engineering and Chemical Engineering and Chemistry, Institute for Complex Molecular Systems