Development of photoactive delivery systems based on polymeric nanofibers for localized therapy against glioblastoma

Glioblastoma is a type of glioma with a low incidence but a high mortality rate due to its malignancy. Current treatments for glioblastoma focus on surgery followed by chemotherapy; however, the systemic administration of antineoplastic drugs damages healthy tissues. For this reason, research is being conducted into their local application and controlled release. Local administration, in conjunction with adjuvant therapies such as photodynamic therapy (PDT), can enhance the therapeutic effect.

Previously, electrospun polymeric nanofibers based on derivates of poly(methyl vinyl ether-alt-maleic anhydride) (PMVEMA) were developed and characterized as efficient drug delivery systems for antineoplastic agents such as doxorubicin (DOX) and carmustine (BCNU). These materials showed encapsulation efficiencies above 80% and a rapid drug release profile, analyzed by HPLC. The passively released drug exhibited a greater therapeutic effect than its free form after 24 hours on glioblastoma patient-derived cell lines (HGUE-GB), while showing low toxicity in human astrocytes. Building on these results, the current work focuses on the functionalization of PMVEMA with photosensitizers (porphyrins) for PDT. Functionalized porphyrins were successfully synthesized and conjugated to PMVEMA (PMVEMA-PS) through a carbodiimide-mediated, microwave-assisted reaction. The coupling was confirmed by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and UV–Vis spectroscopy, yielding a functionalization degree of 54% (w/w). The resulting photoactive polymers are currently being evaluated in glioblastoma spheroids derived from HGUE-GB lines to assess their phototoxic effect and singlet oxygen generation under irradiation.

The functionalized polymers obtained will be incorporated into PMVEMA nanofiber delivery systems together with the antineoplastic drugs. Future studies combining photodynamic therapy and drug release will be conducted in glioblastoma spheroids to evaluate their effect on the tumor microenvironment.