PERFECTA Loaded Lipid Cubosomes for ¹⁹ F‐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 19 F‐MRI nanoprobes. PERFECTA loaded cubosomes were synthesized via solvent evaporation and characterized using DLS, SAXS, Cryo‐TEM, DSC, 19 F ‐NMR, and 19 F ‐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 (T 1 = 497 ± 50 ms, T 2 = 281 ± 4 ms) and robust 19 F MRI signals, these cubosomes hold significant potential as stable, efficient nanotheranostic platforms for biomedical imaging and drug delivery.