Multifunctional folate-targeted cationic magnetoliposomes (FTMLs) have been prepared with co-encapsulated doxorubicin (DOX) and anionic superparamagnetic iron oxide (SPIO) nanoparticles with 5 nm γ-Fe2O3 cores and 16 nm hydrodynamic diameters. Nanoparticle encapsulation (89%) was confirmed by cryogenic transmission electron microscopy, and the presence of the oppositely charged nanoparticles did not cause liposome aggregation. The FTMLs had an average diameter of 174 ± 53 nm and existed as unilamellar and cup-shaped liposomes, which was attributed to dissimilar lipid packing parameters and the presence of PEG-lipids. A 3-fold increase in DOX release was achieved over two hours when the encapsulated SPIO nanoparticles were heated by an alternating current electromagnetic field operating at radiofrequencies (RF). Results with human cervical cancer cells (HeLa), which have been shown to exhibit high folate receptor (FR) expression, confirmed FTML surface binding and cellular uptake. In contrast, no uptake was observed for lower FR-expressing human breast carcinoma cells (ZR-75-1).
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