Quercetin and Rosmarinic Acid Functionalized Hybrid Electrospun Nanofibers with Strong Antioxidant and Anticancer Activities

In this study, novel electrospun polymer mats based on biocompatible poly(lactic acid) (PLA) and hydrophilic poly(ethylene glycol) (PEG) were successfully fabricated for the co-delivery of two natural polyphenols, quercetin (QUE) and rosmarinic acid (RA). Scanning electron microscopy (SEM) revealed the formation of defect-free, continuous nanofibers with high interconnected porosity. By mimicking the structural features of the native extracellular matrix, these nanofibrous platforms facilitate pronounced combined antioxidant and anticancer action. X-ray diffraction (XRD) analysis confirmed that the rapid solvent evaporation during electrospinning induced a physical state transformation, converting both QUE and RA from their native crystalline structures into an amorphous dispersion within the polymer fibrous materials, thereby optimizing their potential bioavailability. The obtained hybrid fibrous materials possessed good mechanical properties. Moreover, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay demonstrated that the incorporation of PEG enhanced matrix hydrophilicity, allowing the four-component PLA/PEG/QUE/RA mats to achieve the highest antioxidant efficiency (98.1%), suggesting an enhanced, complementary radical-neutralization pathway. Furthermore, in vitro biological assessments against human cervical carcinoma cell line (HeLa) and normal murine embryo fibroblasts BALB/3T3 demonstrated prominent anticancer activity, while noncancerous cells were significantly less affected. The dual-loaded PLA/PEG/QUE/RA fibrous mats induced significant cell shrinkage, chromatin condensation, and apoptotic cell death in HeLa cells, while normal BALB/3T3 fibroblasts retained cell membrane integrity and displayed higher resistance. Modeled after the native extracellular matrix, these bioinspired materials demonstrate significant antioxidant and anticancer activity, highlighting their potential for applications in localized cancer therapy, wound management, and tissue engineering.