Abstract
In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 μM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.
Highlights
Development of smart materials that could response to the environmental stimuli is gaining importance over the past decade in the drug delivery system [1]
Figure 1a1 shows the transmission electron microscopy (TEM) image of coated magnetic nanoparticles (CAMNP) which showed a spherical morphology of nanoparticles in the range of 10 nm
Figure 1d1 shows the CAMNP could disperse properly in the aqueous solution and exhibit the interaction with the magnetic exposure (Figure 1d2). This characteristic was generated due to the presence of carboxylic moiety on the surface of magnetic nanoparticles (MNP) (Figure 1e1). Because of their amphiphatic nature of liposomes, doxorubicin (DOX) and CAMNP are expected to be readily incorporated into hydrophilic moiety of liposomes (Figure 1e2)
Summary
Development of smart materials that could response to the environmental stimuli is gaining importance over the past decade in the drug delivery system [1]. Liposomes are synthetic lipid bilayer with enclosed structure up to several hundred nanometers in diameter MNP provided the main advantages of both types of targeting: as with passive targeting, modification of the nanoparticle surface is not necessary, and like active targeting, they can be directed to the site of interest [2]. This is due to the fact that MNP respond strongly to the magnetic fields, and magnetic fields can penetrate human tissue without impediment [24]. MNP have been used as a part of integrating system with liposomes termed as magnetic liposomes or magnetoliposomes [24,25,26]
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