Implantable 5-FU@ZIF-8 core-shell nanofiber fabricated via emulsion electrospinning: a pH-responsive strategy for localized chemotherapy.

Abstract

Localized drug delivery using nanofiber-based systems enables precise and sustained release of chemotherapeutics at tumor sites. In this study, a novel pH-responsive core-shell nanofiber incorporating 5-FU@ZIF-8 was fabricated by o/w emulsion electrospinning using Zein/PVP and black seed oil. SEM analysis confirmed a uniform core-shell morphology (average diameter: 795 ± 16 nm). The 5-FU@ZIF-8-loaded nanofiber (5-FU@ZIF-8 NF) exhibited favorable surface hydrophilicity (39.0° ± 0.7°) and tensile strength (2.07 ± 0.1 MPa). In vitro results demonstrated high biocompatibility (∼90% L929 cell viability) and potent antitumor activity (∼70% CT-26 cytotoxicity), accompanied by increased ROS generation and reduced cell migration. Antibacterial evaluation revealed strong inhibitory activity of 5-FU@ZIF-8 NF against Staphylococcus aureus (55% inhibition), whereas free 5-FU exhibited greater activity against Escherichia coli. In vivo antitumor studies in CT-26 tumor-bearing mice showed a marked reduction in relative tumor volume (RTV ≈ 5 on day 18) and a tumor inhibition rate (TIR) of 70.0 ± 6.57%, with stable body weight and no histopathological abnormalities in liver and kidney tissues (H&E), indicating minimal systemic toxicity. This implantable system offers a precise, localized therapeutic approach with enhanced efficacy and reduced side effects compared to conventional chemotherapy.