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Theranostics 2018; 8(3):693-709. doi:10.7150/thno.21297 This issue Cite

Research Paper

Enhanced Synergism of Thermo-chemotherapy For Liver Cancer with Magnetothermally Responsive Nanocarriers

Minghua Li¹, Wenbo Bu², Jie Ren³, Jianbo Li³, Li Deng³, Mingyuan Gao⁴, Xiaolong Gao¹, Peijun Wang^1✉

1. Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China;
2. School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062,China;
3. Institute of Nano and Biopolymeric Materials, School of Materials, Science and Engineering, Tongji University , Shanghai 201804, China;
4. Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

✉ Corresponding author: Prof. Peijun Wang, Email:wangpeijuntjyyedu.cn

Abstract

A combination of magnetic hyperthermia and magnetothermally-facilitated drug release system was developed as a promising strategy for liver cancer therapy. The thermosensitive copolymer, 6sPCL-b-P(MEO₂MA-co-OEGMA) shows a good temperature-controlled drug release response. Mn-Zn ferrite magnetic nanoparticles (MZF-MNPs) exhibit a strong magnetic thermal effect with an alternating magnetic field (AMF). Owing to its high magnetic sensitivity, the magnetothermally-responsive nanocarrier/doxorubicin (MTRN/DOX) can be concentrated in the tumor site efficiently through magnetic targeting. Given this information, we synthesized MTRN/DOX which was composed of MZF-MNPs, thermosensitive copolymer drug carriers, and the chemotherapeutic drug---DOX, to study its anticancer effects both in vitro and in vivo.

METHODS: MTRN/DOX was designed and prepared. Firstly, we investigated the accumulation effects of MTRN/DOX by Prussian blue staining, transmission electron microscopy (TEM), laser scanning confocal microscopy (LSCM) and conducted 7.0 T MRI. Following this, the magnetothermal effects of MTRN/DOX were studied using an infrared thermal camera. DOX uptake, distribution, and retention in tumor cells and the distribution of MTRN/DOX in vivo were then analyzed via LSCM, flow cytometry and live fluorescence imaging. Lastly, its anticancer effects were evaluated by MTT, AM/PI staining, Annexin-VFITC/PI staining and comparison of relative tumor volume.

RESULTS: We found that MTRN/DOX can be efficiently concentrated in the tumor site through magnetic targeting, increasing the uptake of DOX by tumor cells, and prolonging the retention time of the drug within the tumors. MTRN/DOX showed good magnetothermal effects both in vitro and in vivo. Based on the above results, MTRN/DOX had significant anticancer effects.

CONCLUSIONS: MTRN/DOX causes temporal-spatial synchronism of thermo-chemotherapy and together with chemotherapeutic drugs, produces a synergistic effect, which enhances the sensitivity of tumor cells to DOX and reduces their side effects.

Keywords: Magnetic nanoparticles, Magnetic hyperthermia, Magnetic target, Drug delivery, Cancer combined therapy.

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