Localized microrobotic delivery of enzyme-responsive hydrogel-immobilized therapeutics to suppress triple-negative breast cancer
Author(s)
Tian, Mingzhen
Keshavarz, Meysam
Demircali, Ali Anil
Han, Bing
Yang, Guang-Zhong
Type
Journal Article
Abstract
Triple-negative breast cancer (TNBC), characterized by its aggressive metastatic propensity and lack of effective targeted therapeutic options, poses a major challenge in oncological management. A proof-of-concept neoadjuvant strategy aimed at inhibiting TNBC tumor growth and mitigating metastasis through a localized delivery of chemotherapeutics is reported in this paper. This approach addresses the limitations in payload capacity and stimuli responsiveness commonly associated with microrobotics in oncology. A hydrogel-based system is developed for the immobilization of chemotherapeutic agents, subsequently encapsulated within magnetically responsive microrobots. This design leverages external magnetic fields to facilitate the precise navigation and localization of the therapeutic agents directly to the tumor site. The efficacy of this approach is demonstrated in an animal model, in which a significant 14-fold reduction in tumor size and suppression of metastasis to critical organs such as the liver and lungs are observed. Crucially, the drug release mechanism is engineered to be responsive to the tumor microenvironment and is regulated by the overexpression of the enzymatic activity of matrix metalloproteinases (MMP2 and MMP9) in TNBC tumors, triggering the degradation of the hydrogel matrix, leading to controlled release of the immobilized therapeutic drug. This ensures that the therapeutic action is localized, reducing systemic toxicity and enhancing treatment efficacy. These findings suggest that this neoadjuvant approach holds promise for broader applications in other cancer types.
Date Issued
2025-05-05
Date Acceptance
2024-12-01
Citation
Small, 2025, 21 (18)
ISSN
1613-6810
Publisher
Wiley
Journal / Book Title
Small
Volume
21
Issue
18
Copyright Statement
© 2024 The Author(s). Small published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39692188
Subjects
Chemistry
Chemistry, Multidisciplinary
Chemistry, Physical
controlled release
drug delivery systems
hydrogel carriers
localized therapy
Materials Science
Materials Science, Multidisciplinary
microrobots
NANOPARTICLES
Nanoscience & Nanotechnology
Physical Sciences
Physics
Physics, Applied
Physics, Condensed Matter
RELEASE
Science & Technology
Science & Technology - Other Topics
SURFACE
Technology
THERAPY
triple-negative breast cancer
tumor microenvironment
Publication Status
Published
Coverage Spatial
Germany
Article Number
2408813
Date Publish Online
2024-12-18