PERFECTA Loaded Lipid Cubosomes for ¹⁹F-MRI: Physico-Chemical Characterization

Liquid crystalline nanoparticles (LCNPs), such as cubosomes, are promising platforms for drug delivery and bioimaging due to their unique internal structures and biocompatibility. Here, we developed phytantriol-based cubosomes stabilized with Pluronic F-127 and loaded with PERFECTA, a fluorinated probe with 36 magnetically equivalent fluorine atoms, for use as ¹⁹F-MRI nanoprobes. PERFECTA loaded cubosomes were synthesized via solvent evaporation and characterized using DLS, SAXS, Cryo-TEM, DSC, ¹⁹F -NMR, and ¹⁹F -MRI. Results show that PERFECTA-loaded cubosomes retain the Pn3m cubic phase, achieving encapsulation efficiencies over 70% across PERFECTA concentrations (1-10 mg/mL). Cryo-TEM revealed PERFECTA segregation into spherical domains, either embedded within cubosomes or as isolated nanoparticles. SAXS and DSC analyses suggested a partial PERFECTA integration into the phytantriol bilayer, affecting the internal liquid-crystalline order. PERFECTA loaded cubosomes demonstrated excellent colloidal stability in biologically relevant media, maintaining structural integrity and fluorine content within 24 h in cell culture medium with fetal bovine serum. Thanks to their favorable relaxometric properties (T₁ = 497 ± 50 ms, T₂ = 281 ± 4 ms) and robust ¹⁹F MRI signals, these cubosomes hold significant potential as stable, efficient nanotheranostic platforms for biomedical imaging and drug delivery.