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Conformable hierarchically engineered polymeric micromeshes enabling combinatorial therapies in brain tumours
Daniele Di Mascolo1, Anna Lisa Palange1, Rosita Primavera1,2
1Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy.
Nature Nanotechnology
|April 2, 2021
Summary
A novel biodegradable implant, micro-mesh (μMESH), delivers drugs directly to brain tumor sites, preventing recurrence and improving survival in glioblastoma models. This flexible mesh offers a promising new strategy for localized cancer treatment.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Oncology
Background:
- Glioblastoma multiforme (GBM) poses a poor prognosis due to challenges in drug delivery across the blood-brain barrier and tumor heterogeneity.
- Effective localized treatment strategies are crucial for improving outcomes in GBM patients.
Purpose of the Study:
- To engineer a biodegradable implant (μMESH) for direct, sustained drug delivery to the tumor bed after resection.
- To evaluate the efficacy of μMESH in preventing glioblastoma recurrence and improving survival in preclinical models.
Main Methods:
- Fabrication of a flexible, biodegradable poly(lactic-co-glycolic acid) mesh (μMESH) over a water-soluble poly(vinyl alcohol) layer.
- Loading of docetaxel-loaded nanomedicines and diclofenac molecules into the μMESH for controlled release.
- In vivo testing in orthotopic brain cancer models using both cell line and patient-derived cells, with and without tumor resection.
Main Results:
- A single μMESH application prevented disease recurrence for up to eight months post-resection in orthotopic models with no significant adverse effects.
- In non-resected models, μMESH significantly increased median overall survival compared to conventional docetaxel nanomedicines or systemic temozolomide.
- The μMESH demonstrated successful co-delivery of docetaxel and diclofenac, showcasing its potential for modular drug loading.
Conclusions:
- The μMESH is a promising biodegradable implant for localized, sustained drug delivery in glioblastoma treatment.
- Its flexible, modular design allows for patient-specific dosing and potential application in various cancer types.
- μMESH represents a significant advancement in overcoming drug delivery challenges in brain cancer therapy.
