Pegylated hollow gold-mitoxantrone nanoparticles combining photodynamic therapy and chemotherapy of cancer cells

Abstract

Background: In recent years, Mitoxantrone (MTX) has been introduced as a chemotherapy drug which also serves as a photosensitizer and radiosensitizer. Due to its serious side effects, there are limitations to the application of MTX so scientists are looking for solutions to overcome this problem. Hollow gold nanoparticles (HAuNP) have attracted growing attention due to their unique physical-chemical properties, such as biocompatibility, tunable plasmonic absorption peak ranging from visible to near infrared, high stability and various medical applications in imaging, drug delivery and combinational cancer treatments. In this paper, the combinational effect of photodynamic therapy (PDT) and chemotherapy of MTX conjugated to HAuNP is studied.

Method: After optimizing the synthesis of PEGylated HAuNP and preparing nanostructures conjugated with MTX, the characteristics of pharmacological agents including MTX, HAuNP, mPEG-HAuNP,and MTX-mPEG-HAuNP and their toxicity were determined at different concentrations on two cell lines of DFW and MCF7 derived from human melanoma and breast cancer, respectively. To select the optimal concentration for PDT, the cytotoxicity of agents was investigated at concentrations of 3, 6, 9 and 12 μM. Moreover, a LEDs system at 630 nm and power output of 3 W was used to apply PDT process. MTT test was used to determine cell survival 24 h after treatment. Several indexes were utilized for data comparison, such as therapeutic efficacy (TE), necessary concentration to kill 50% of cells (IC₅₀), and necessary light exposure to induce 50% cell death (ED₅₀).

Results: LED exposure alone did not cause significant cell death. For MTX-mPEG-HAuNP, at both cell lines, IC₅₀ had the least exposure to dark condition with an exposure time of less than 9 min and this nanostructure had the smallest ED₅₀ in each cell line at all concentrations. TE of MTX-mPEG-HAuNP at different exposures and concentrations was greater than 1 for the DFW cells. It was also true for concentrations greater than 6 μM with irradiation times longer than 3 min for MCF7 cells.

Conclusion: This is the first paper to use PEGylated hollow gold nanoparticles as the nanocarrier for MTX. The results indicated that MTX-mPEG-HAuNP improved the efficacy of PDT with Light Emission diode.

Keywords: Hollow gold nanoshell; Mitoxantrone; Photodynamic therapy.