Synergistic Theranostics of Magnetic Resonance Imaging and Photothermal Therapy of Breast Cancer Based on the Janus Nanostructures Fe(3)O(4)-Au(shell)-PEG

基于Janus纳米结构Fe(3)O(4)-Au(shell)-PEG的乳腺癌磁共振成像与光热疗法的协同诊疗

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Abstract

BACKGROUND: Satisfactory prognosis of breast cancer (BC) is limited by difficulty in early diagnosis and insufficient treatment. The combination of molecular imaging and photothermal therapy (PTT) may provide a solution. METHODS: Fe(3)O(4)-Au(shell) nanoparticles (NPs) were prepared by thermal decomposition, seeded growth and galvanic replacement and were comprehensively characterized. After conjugated to PEG, NPs were used as MRI and PTT agents in vitro and in vivo. RESULTS: Fe(3)O(4)-Au(shell) NPs which had uniform Janus-like morphology were successfully synthesized. The Fe(3)O(4) had a size of 18 ± 2.2 nm, and the Au(shell) had an outer diameter of 25 ± 3.3 nm and an inner diameter of 20 ± 2.9 nm. The NPs showed superparamagnetism, a saturation magnetization of 36 emu/g, and an optical absorption plateau from 700 to 808 nm. The Fe(3)O(4)-Au(shell) NPs were determined to possess good biocompatibility. After PEG coating, the zeta potential of NPs was changed from -23.75 ± 1.37 mV to -13.93 ± 0.55 mV, and the FTIR showed the characteristic C-O stretching vibration at 1113 cm(-1). The NPs' MR imaging implied that the T(2) can be shortened by Fe(3)O(4)-Au(shell) NPs in a concentration-dependent manner, and the Fe(3)O(4)-Au(shell) NPs coated with PEG at the molar ratio of 160 (PEG: NPs) showed the highest transverse relaxivity (r (2)) of 216 mM(-1)s(-1). After irradiation at 0.65 W/cm(2) for 5 min, all cells incubated with the Fe(3)O(4)-Au(shell)-PEG160 NPs (Fe: 30 ppm, Au: 70 ppm) died. After administrated intratumorally, Fe(3)O(4)-Au(shell)-PEG160 notably decreased the signal intensity of tumor in T(2)WI images. Under the same irradiation, the temperature of tumors injected with Fe(3)O(4)-Au(shell)-PEG160 quickly rose to 54.6°C, and the tumors shrank rapidly and were ablated in 6 days. CONCLUSION: Fe(3)O(4)-Au(shell)-PEG NPs show good r (2) and PTT performance and are promising synergistic theranostic agents of MRI and PTT for BC.

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