title: A visualized investigation at the atomic scale of the antitumor effect of magnetic nanomedicine on gastric cancer cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Second Clinical Medical School of Lanzhou University, the Second Hospital of Lanzhou University, Lanzhou 730030, China.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Liu
authors.forename: Xia
authors.initials: X
authors.lastname: Deng
authors.forename: Xinghua
authors.initials: X
authors.lastname: Li
authors.forename: Desheng
authors.initials: D
authors.lastname: Xue
authors.forename: Haoli
authors.initials: H
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Qingfang
authors.initials: Q
authors.lastname: Liu
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Mellors
authors.forename: Yumin
authors.initials: Y
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D017348:Microscopy, Electron, Scanning Transmission; D008928:Mitochondria / Q000187:drug effects; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D050997:Nanomedicine; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D058726:Nanoconjugates; D002266:Carboxymethylcellulose Sodium; D005472:Fluorouracil
keywords: Fe3O4–carboxymethyl cellulose–5-fluorouracil nanomedicine; STEM; antitumor effect; elemental mapping; gastric cancer cell