RT Journal Article
T1 Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
A1 González Prada, Iago
A1 Barcelos Ribeiro, Arthur
A1 Dion, Marine
A1 Magariños Ferro, Beatriz
A1 Lapoujade, Clémentine
A1 Rousseau, Audrey
A1 Concheiro Nine, Ángel Joaquín
A1 Garcion, Emmanuel
A1 Álvarez Lorenzo, Carmen
K1 Copper
K1 Cyclodextrin
K1 Disulfiram
K1 Electrospinning
K1 Glioblastoma
K1 Silk fibroin
AB Glioblastoma (GB) is a malignant brain tumor with low survival rates and a high recurrence ratio due to limited therapeutic arsenal. The repurposed drug disulfiram (DSF), approved for alcoholism treatment, shows promising anticancer and antimicrobial activity, but its poor biopharmaceutical profile hinders its clinical use. This work aimed to develop DSF-loaded silk fibroin (SF) electrospun fibers for controlled release in the postsurgical resection cavity. Incorporating hydroxypropyl-β-cyclodextrin (HPβCD), which formed inclusion complexes with DSF, enhanced drug release rate and antimicrobial activity (>3 logCFUs reduction) against Staphylococcus aureus and Pseudomonas aeruginosa. Addition of CuCl2 enabled in situ formation of Cu(DDC)2 complexes, further boosting antimicrobial and in vitro antitumoral effects of the nanofibers (≤ 500 nm) while maintaining adequate mechanical properties. Selective toxicity of DSF and DSF-loaded fibers against glioblastoma cells, while sparing against astrocytes, highlights the potential of the nanofibers for targeted brain cancer therapy. Increased potency of DSF at low concentrations when combined with SF fibers, HPβCD and copper was remarkable. Thus, DSF delivery and bioavailability can be significantly optimized through electrospun nanofibers, which may also allow for more precise dosing. Combination with radiotherapy was also explored to assess the translational potential of DSF as part of a combination therapy regimen for glioblastoma. In vivo studies in a rat model simulating GB surgery confirmed the safety of selected formulations in healthy brain tissue. However, findings suggest that DSF-loaded fibers alone may be insufficient for complete tumor eradication, indicating the need for combination with existing therapies to target residual tumor cells effectively.
PB Elsevier
SN 0168-3659
YR 2025
FD 2025-03-12
LK https://hdl.handle.net/10347/46977
UL https://hdl.handle.net/10347/46977
LA eng
NO Gonzalez-Prada, I., Barcelos Ribeiro, A., Dion, M., Magariños, B., Lapoujade, C., Rousseau, A., Concheiro, A., Garcion, E., & Alvarez-Lorenzo, C. (2025). Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment. Journal of Controlled Release, 381. https://doi.org/10.1016/J.JCONREL.2025.113615
NO The work was supported by MCIN [PID 2020-113881RB-I00/AEI/10.13039/501100011033], Spain, FEDER, Xunta de Galicia [ED431C 2024/09], the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Angers and by the French National Agency for Research (ANR) under the frame of EuroNanoMed III (project GLIOSILK) [ANR-19-ENM3-0003-01] (to EG and CAL), and the “France 2030 Investment Plan” Labex Iron [ANR-11-LABX-18- 01] (to EG, funding of MD). It was additionally related to: the “Région Pays-de-la-Loire” under the frame of the Target'In project (to EG); the “Ligue Nationale contre le Cancer” and the “Comité Départemental de Maine-et-Loire de la Ligue contre le Cancer” (CD49) under the frame of the FusTarG project (to EG) and the “Tumour targeting, imaging and radio-therapies network” of the “Cancéropôle Grand-Ouest” (France).
DS Minerva
RD 22 may 2026