Synthesis-dependent structure and anticancer activity of 5-fluorouracil-loaded praseodymium selenide nanoparticles

Praseodymium selenide nanoparticles (NPs) were fabricated via two hydrothermal approaches: in situ β-cyclodextrin citrate incorporation (method 1) and post-synthesis coating (method 2). X-ray diffraction confirmed tetragonal crystallinity, while transmission electron microscopy revealed rod-like particles averaging 13±5 nm in length (width≈5±2 nm) in method 1 and 425±50 nm in length (width≈59±10 nm) in method 2. Infrared, X-ray photoelectron and thermogravimetric analyses verified successful surface functionalization, with organic contents of ~38% (method 1) and ~32% (method 2). Both systems achieved high 5-fluorouracil (5-FU) encapsulation efficiencies (90% and 88%, respectively) and pH-responsive release, with >90% drug liberation under mildly acidic conditions within 48 h. Cytotoxicity assays against MCF-7 breast cancer cells yielded IC₅₀ values of 14.1±3.2 µg/mL (empty) and 9.4±0.4 µg/mL (drug-loaded) in method 1, and 35.0±3.1 µg/mL (empty) and 8.7±0.4 µg/mL (drug-loaded) in method 2. Enhanced activity correlated with increased reactive oxygen species (ROS) generation, mitochondrial membrane depolarization and nuclear condensation, indicative of apoptosis. Non-cancerous 3T3 fibroblasts displayed minimal susceptibility (IC₅₀>100 µg/mL in method 2). These results position β-CD-citrate-modified Pr₂Se₃ nanoparticles as tunable, biocompatible and highly effective drug delivery platforms for targeted breast cancer therapy.