Conformable hierarchically engineered polymeric micromeshes enabling combinatorial therapies in brain tumours.

Autor: Di Mascolo D; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy., Palange AL; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy., Primavera R; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy.; Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA, USA., Macchi F; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy., Catelani T; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy.; Microscopy Facility, University of Milano-Bicocca, Milan, Italy., Piccardi F; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy., Spanò R; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy., Ferreira M; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy., Marotta R; Electron Microscopy Facility, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy., Armirotti A; Analytical Chemistry Lab, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy., Gallotti AL; Neural Stem Cell Biology Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy., Galli R; Neural Stem Cell Biology Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy., Wilson C; Department of Neurosurgery, Stanford University, Palo Alto, CA, USA., Grant GA; Department of Neurosurgery, Stanford University, Palo Alto, CA, USA., Decuzzi P; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy. paolo.decuzzi@iit.it.
Jazyk: angličtina
Zdroj: Nature nanotechnology [Nat Nanotechnol] 2021 Jul; Vol. 16 (7), pp. 820-829. Date of Electronic Publication: 2021 Apr 01.
DOI: 10.1038/s41565-021-00879-3
Abstrakt: The poor transport of molecular and nanoscale agents through the blood-brain barrier together with tumour heterogeneity contribute to the dismal prognosis in patients with glioblastoma multiforme. Here, a biodegradable implant (μMESH) is engineered in the form of a micrometre-sized poly(lactic-co-glycolic acid) mesh laid over a water-soluble poly(vinyl alcohol) layer. Upon poly(vinyl alcohol) dissolution, the flexible poly(lactic-co-glycolic acid) mesh conforms to the resected tumour cavity as docetaxel-loaded nanomedicines and diclofenac molecules are continuously and directly released into the adjacent tumour bed. In orthotopic brain cancer models, generated with a conventional, reference cell line and patient-derived cells, a single μMESH application, carrying 0.75 mg kg -1 of docetaxel and diclofenac, abrogates disease recurrence up to eight months after tumour resection, with no appreciable adverse effects. Without tumour resection, the μMESH increases the median overall survival (∼30 d) as compared with the one-time intracranial deposition of docetaxel-loaded nanomedicines (15 d) or 10 cycles of systemically administered temozolomide (12 d). The μMESH modular structure, for the independent coloading of different molecules and nanomedicines, together with its mechanical flexibility, can be exploited to treat a variety of cancers, realizing patient-specific dosing and interventions.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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