Anti‐Estrogen‐Loaded Superparamagnetic Liposomes for Intracellular Magnetic Targeting and Treatment of Breast Cancer Tumors

Abstract The selective delivery of the steroid anti‐estrogen RU 58668 (RU) to human breast cancer MCF‐7 cells by using nanoscaled hybrid liposomes, labelled with rhodamine, coated by poly(ethylene glycol) and entrapping superparamagnetic nanocrystals of maghemite (γ‐Fe₂O₃) was investigated. Stable drug incorporation within the vesicle bilayer was ascertained by differential scanning calorimetry and small‐angle X‐ray diffraction. The study of the interactions with living tumor cells of the magnetic‐fluid‐loaded liposomes containing RU molecules (RU‐MFLs) showed a significant improvement in RU‐MLF uptake through their guidance by a magnetic field gradient of 155 T m⁻¹ produced by a 0.44 T external magnet placed in the near vicinity of the cells. RU‐MFLs enter the cells by endocytosis, as revealed by electron microscopy, and greatly accumulate therein as intact structures, as supported by confocal fluorescence microscopy images, which revealed a lipid vesicle pathway, as well as by independent iron oxide quantification by magnetophoresis or electron spin resonance. Inhibition assay of estradiol‐induced transcription of the luciferase reporter gene in MELN cells confirmed that RU anti‐estrogenic activity was entirely preserved upon its liposome‐mediated intracellular uptake. This work provides a proof of concept of intracellular magnetic targeting of a therapeutic substance by means of superparamagnetic liposomes, which is especially promising as a tool for cancer therapy.