Bio‐Propelled Stomatocyte Nanomotors with Glutathione‐Responsiveness for Osteoarthritis Treatment
Abstract
ABSTRACT Pharmacological intervention is a primary therapeutic strategy for Osteoarthritis (OA), however, improving the bioavailability of therapeutic agents remains a significant challenge. In this study, we developed oxygen‐propelled, glutathione (GSH)‐responsive stomatocyte nanomotors (MTX/MnO 2 ‐GSH‐stomatocytes) for osteoarthritis (OA) treatment. First, polymersomes were assembled composed of block copolymers containing a GSH‐cleavable disulfide linker, which were loaded with the therapeutic agent methotrexate (MTX) into their hydrophilic domain. Upon dialysis‐induced shape change bowl shaped stomatocytes were formed with manganese dioxide (MnO 2 ) particles encapsulated into the nanocavity with high loading efficiency. Within the OA microenvironment, MnO 2 decomposed the inflammatory hydrogen peroxide (H 2 O 2 ), generating an O 2 gradient that propelled the nanomotors and enabled chemotactic movement for targeted cargo delivery. Meanwhile, after cellular uptake elevated GSH levels cleaved the disulfide linkers, inducing the collapse of the stomatocyte structure and the rapid release of MTX. The motility and targeted release behavior of the nanomotors were systematically evaluated both in vitro and in vivo. Experimental results demonstrated that these nanomotors effectively alleviated oxidative stress, inflammation, and cartilage degradation, while exhibiting negligible adverse effects. Overall, this study presents a promising GSH‐responsive, nanomotor‐based strategy for enhanced osteoarthritis therapy.
Article Details
Authors (13)
Jianhong Wang
Bio-Organic Chemistry, Departments of Biomedical Engineering and Chemical Engineering and Chemistry, Institute for Complex Molecular Systems
Mengsi Zhan
Hanglong Wu
Maarten Bransen
Laboratory of Physical Chemistry and Center for Multiscale Electron Microscopy, Department of Chemical Engineering and Chemistry and Institute for Complex Molecular Systems
Ioanna Balmpouzi
Bio‐Organic Chemistry Department of Biomedical Engineering Institute For Complex Molecular Systems (ICMS) Eindhoven University of Technology Eindhoven The Netherlands
Xianwen Lou
Institute for Complex Molecular Systems
Junjie Liu
Institute of Molecular Physiology
Nina Wang
Zhiqiang Wang
Heiner Friedrich
Laboratory of Physical Chemistry and Center for Multiscale Electron Microscopy, Department of Chemical Engineering and Chemistry and Institute for Complex Molecular Systems
Jingxin Shao
Bio-Organic Chemistry, Institute for Complex Molecular Systems (ICMS)
Jan C. M. van Hest
Bio-Organic Chemistry, Departments of Biomedical Engineering and Chemical Engineering and Chemistry, Institute for Complex Molecular Systems
Xiangyang Shi
State Key Laboratory of Advanced Fiber Polymer Materials Shanghai Engineering Research Center of Nano‐Biomaterials and Regenerative Medicine College of Biological Science and Medical Engineering Donghua University Shanghai P. R. China