Multifunctional liposomal drug delivery with dual probes of magnetic resonance and fluorescence imaging

Many liposomal drug carriers have shown great promise in the clinic. To ensure the efficient preclinical development of drug-loaded liposomes, the drug retention and circulation properties of these systems should be characterized. Iron oxide (Fe₃O₄) magnetic nanoparticles (MNPs) are used as T2 contrast agents in magnetic resonance imaging (MRI). Gold nanoclusters (GNCs) contain tens of atoms with subnanometer dimensions; they have very low cytotoxicity and possess superb red emitting fluorescent properties, which prevents in vivo background autofluorescence. The aim of this study was to develop dual imaging, nanocomposite, multifunctional liposome drug carriers (Fe₃O₄-GNCs) comprising MNPs of iron oxide and GNCs. First, MNPs of iron oxide were synthesized by co-precipitation. The MNP surfaces were modified with amine groups using 3-aminopropyltriethoxysilane (APTES). Second, GNCs were synthesized by reducing HAuCl₄·3H₂O with NaBH4 in the presence of lipoic acid (as a stabilizer and nanosynthetic template). The GNCs were grown by adsorption onto particles to control the size and stability of the resultant colloids. Subsequently, dual Fe₃O₄-GNCs imaging probes were fabricated by conjugating the iron oxide MNPs with the GNCs via amide bonds. Finally, liposome nanocarriers were used to enclose the Fe₃O₄-GNCs in an inner phase (liposome@Fe₃O₄-GNCs) by reverse phase evaporation. These nanocarriers were characterized by dynamic light scattering (DLS), fluorescence spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectrophotometry, superconducting quantum interference device (SQUID), nuclear magnetic resonance (NMR) imaging and in vivo imaging systems (IVIS). These multifunctional liposomal drug delivery systems with dual probes are expected to prove useful in preclinical trials for cancer diagnosis and therapy.