Polymer Fibers Embedded with Small Molecule Drug and Copper Oxide Nanoparticles for Synergistic Local Cancer Therapy of Glioblastoma

Glioblastoma multiforme (GBM), the most common but aggressive primary tumor of the central nervous system, has been investigated for many years but still persists with minimal improvement in the median survival of < 24 months.¹ Developing effective treatments for GBM is very challenging because of its highly invasive nature, immunosuppressive tumor microenvironment, evasive cancer stem-cell population, and cellular heterogeneity. Standard care typically involving surgical tumor resection followed by radiation and chemotherapy, often falls short of fully eradicating the disease, as residual tumor cells, particularly tumor-initiating cells (TICs), frequently lead to recurrence and progression. To address various mechanisms of GBM recurrence and growth, a multifaceted therapeutic approach is essential which can simultaneously target and block the various pathways that promote GBM cell survival and proliferation. Significantly, because GBM recurrence occurs primarily near the original lesion area (within ~2 cm), effective local therapy will positively impact GBM treatments.²
In this study, a localized drug delivery vehicle for the GBM therapy was demonstrated using coaxially electrospun core-sheath nanofibers embedding copper oxide nanoparticles (CuO NPs) and acriflavine (ACF), a hypoxia-inducible factor (HIF) inhibitor. Coaxial electrospinning is a versatile method to produce the core-sheath fibers loaded with various active components that can be released in a controlled manner.³ The combination of ACF and CuO NPs incorporated in coaxial fibers aims to provide synergistic dual-action therapy to effectively target tumor-initiating cells, while inhibiting key downstream factors of GBM growth, such as immune suppression, angiogenesis, metabolism, proliferation, invasion, and migration.
Acetate-capped CuO NPs chemically synthesized in water⁴ were redispersed in an organic solvent following solvent exchange process for successful incorporation into electrospun fibers. Transmission electron microscopy with energy-dispersive spectroscopy elemental mapping confirmed uniform NPs distribution within the fiber core. Fourier-transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) presented no adverse interactions between CuO NPs and ACF, or any chemical interaction with the host polymers, which should facilitate a faster release of therapeutic agents while maintaining effective bioavailability against GBM. Cytotoxicity assays indicate synergistic effects between the two compounds leading to significant dose reduction compared to individual drug treatment.

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