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Localized Microrobotic Delivery of Enzyme-Responsive Hydrogel-Immobilized Therapeutics to Suppress Triple-Negative
Mingzhen Tian1, Meysam Keshavarz2, Ali Anil Demircali3
1Institute of Medical Robotics, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
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.
Insights
This study presents a novel microrobot system for targeted chemotherapy delivery in triple-negative breast cancer (TNBC). The system significantly reduced tumor size and metastasis, offering a promising localized treatment strategy.
Area of Science:
- Oncology
- Biomedical Engineering
- Materials Science
Background:
- Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
- Microrobotics face challenges in drug payload capacity and targeted delivery.
- Localized chemotherapy delivery is crucial for improving TNBC treatment efficacy and reducing toxicity.
Purpose of the Study:
- To develop and evaluate a novel microrobot-based neoadjuvant chemotherapy delivery system for TNBC.
- To enhance targeted drug delivery to the tumor site while minimizing systemic exposure.
- To investigate the potential of this system in inhibiting tumor growth and metastasis.
Main Methods:
- Development of a hydrogel-based system for chemotherapeutic immobilization.
- Encapsulation of hydrogel-drug complexes within magnetically responsive microrobots.
- Utilizing external magnetic fields for precise microrobot navigation and tumor localization.
- Engineering a tumor microenvironment-responsive drug release mechanism triggered by MMP2/MMP9 activity.
Main Results:
- Demonstrated significant tumor size reduction (14-fold) in an animal model.
- Observed suppression of metastasis to vital organs like the liver and lungs.
- Confirmed localized and controlled drug release mediated by the tumor microenvironment.
Conclusions:
- The developed microrobot system shows significant potential as a neoadjuvant therapy for TNBC.
- This localized, stimuli-responsive drug delivery approach effectively inhibits tumor growth and metastasis.
- The strategy holds promise for application in other cancer types with similar microenvironmental characteristics.
