Research Article

A visualized investigation at the atomic scale of the antitumor effect of magnetic nanomedicine on gastric cancer cells

The Second Clinical Medical School of Lanzhou University, the Second Hospital of Lanzhou University, Lanzhou 730030, China

Chinese Armed Police Force General Hospital of Gansu Province, Lanzhou 730000, China

^‡These authors contributed equally

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Xia Deng^‡

Key Laboratory of Magnetism & Magnetic Materials of Ministry of Education, Lanzhou University, Lanzhou 730000, China

^‡These authors contributed equally

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Xinghua Li

Key Laboratory of Magnetism & Magnetic Materials of Ministry of Education, Lanzhou University, Lanzhou 730000, China

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Desheng Xue

Key Laboratory of Magnetism & Magnetic Materials of Ministry of Education, Lanzhou University, Lanzhou 730000, China

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Haoli Zhang

State Key Laboratory of Applied Organic Chemistry, College of Chemistry & Chemical Engineering, Lanzhou University, Lanzhou 730000, China

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Tao Liu

The Second Clinical Medical School of Lanzhou University, the Second Hospital of Lanzhou University, Lanzhou 730030, China

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Qingfang Liu

Key Laboratory of Magnetism & Magnetic Materials of Ministry of Education, Lanzhou University, Lanzhou 730000, China

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Nigel J Mellors

Nano Materials Group, School of Computing, Science & Engineering, University of Salford, Greater Manchester, M5 4WT, UK

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Yumin Li^‡

* Authors for correspondence:

E-mail Address: liym@lzu.edu.cn

E-mail Address: pengy@lzu.edu.cn

The Second Clinical Medical School of Lanzhou University, the Second Hospital of Lanzhou University, Lanzhou 730030, China

^‡These authors contributed equally

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Yong Peng^‡,

* Authors for correspondence:

E-mail Address: liym@lzu.edu.cn

E-mail Address: pengy@lzu.edu.cn

Key Laboratory of Magnetism & Magnetic Materials of Ministry of Education, Lanzhou University, Lanzhou 730000, China

^‡These authors contributed equally

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Published Online:10 Sep 2014https://doi.org/10.2217/nnm.13.142

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Abstract

Aim: Discovering which anticancer drugs attack which organelle(s) of cancer cells is essential and significant, not only for understanding their therapeutic and adverse effects, but also to enable the development of new-generation therapeutics. Here, we show that novel Fe₃O₄–carboxymethyl cellulose–5-fluorouracil (Fe₃O₄–CMC–5FU) nanomedicine can apparently enhance the antitumor effect on gastric cancer cells, and its mechanism of killing the SGC-7901 gastric cancer cells can be directly observed at the atomic scale. Materials & methods: The novel nanomedicine was prepared using the traditional antitumor drug 5FU to chemically bond onto the functionalized Fe₃O₄ nanoparticles (Fe₃O₄–CMC–5FU nanomedicine), and then was fed into SGC-7901 gastric cancer cells. The inorganic Fe₃O₄ nanoparticles were used to track the distribution and antitumor effect of the nanomedicine within individual SGC-7901 gastric cancer cells. Results & discussion: Atomic-level observation and tracking the elemental distribution inside individual cells proved that the magnetic nanomedicine killed the gastric cells mainly by attacking their mitochondria. The enhanced therapeutic efficacy derives from the localized high concentration and poor mobility of the aggregated Fe₃O₄–CMC–5FU nanomedicine in the cytoplasm. Conclusion: A brand new mechanism of Fe₃O₄–CMC–5FU nanomedicine killing SGC-7901 gastric cancer cells by attacking their mitochondria was discovered, which is different from the classical mechanism utilized by traditional medicine 5FU, which kills gastric cancer cells by damaging their DNA. Our work might provide a partial solution in nanomedicines or even modern anticancer medicine for the visualized investigation of their antitumor effect.

Original submitted 25 January 2013; Revised submitted 10 May 2013

Keywords:

Papers of special note have been highlighted as: • of interest •• of considerable interest

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Vol. 9, No. 9

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Published online 10 September 2014

Published in print July 2014

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Keywords

Author contributions

Y Peng designed the experiments, performed part of transmission electron microscopy measurements, provided overall guidance, supervised the project, analyzed and interpreted the data, and wrote the manuscript. X Liu and X Deng performed the experiments, analyzed the data, prepared all of the figures and the table, and provided assistance in writing the manuscript. Y Li supervised the biological experiments and supervised the project. X Li guided the preparation of size- and shape-controlled Fe3O4 nanoparticles. D Xue, H Zhang and Q Liu supervised the project. T Liu provided assistance in cell culture. NJ Mellors revised the English. All authors discussed the results and commented on the manuscript.

Financial & competing interests disclosure

This work was supported by the National Basic Research Program of China (2012CB93310X), National Natural Science Foundation of China (11274145 and 11034004), Natural Science Foundation of Gansu Province in China (1107RJZA221) and Fundamental Research Funds for the Central Universities (lzujbky-2013–19 and lzujbky-2012–226). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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