Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine

Int J Nanomedicine. 2013:8:2443-51. doi: 10.2147/IJN.S46327. Epub 2013 Jul 10.

Abstract

Immunohistochemistry and an immunofluorescence technique was used to detect folate receptor expression in tissue samples and cell lines of head and neck squamous carcinoma, including 20 tissue samples of nasopharyngeal carcinoma, 16 tissue samples of laryngeal carcinoma, and HNE-1, HNE-2, CNE-1, CNE-2, SUNE-1, 5-8F, and Hep-2 cell lines. Iron staining, electron microscopy, and magnetic resonance imaging were used to observe endocytosis of folate-conjugated cisplatin-loaded magnetic nanoparticles (CDDP-FA-ASA-MNP) in cultured cells and transplanted tumors. As shown by immunohistochemistry, 83.3% (30/36) of the head and neck squamous carcinomas expressed the folate receptor versus none in the control group (0/24). Only the HNE-1 and Hep-2 cell lines expressed the folate receptor, and the other five cell lines did not. Endocytosis of CDDP-FA-ASA-MNP was seen in HNE-1 and Hep-2 cells by iron staining and electron microscopy. A similar result was seen in transplanted tumors in nude mice. Magnetic resonance imaging showed low signal intensity of HNE-1 cells and HNE-1 transplanted tumors on T2-weighted images after uptake of CDDP-FA-ASA-MNP, and this was not seen in CNE-2 transplanted tumors. In conclusion, head and neck squamous carcinoma cell strongly expressed the folate receptor, while normal tissue did not. The folate receptor can mediate endocytosis of folate-conjugated anticancer nanomedicines, and lays the foundation for molecular targeted treatment of cancer.

Keywords: cisplatin; folate receptor; laryngeal carcinoma; molecular targeting; nanomedicine; nasopharyngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Carcinoma
  • Cell Line, Tumor
  • Chi-Square Distribution
  • Cisplatin / chemistry
  • Cisplatin / pharmacokinetics
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics*
  • Endocytosis
  • Female
  • Folate Receptors, GPI-Anchored / metabolism*
  • Humans
  • Laryngeal Neoplasms / chemistry
  • Laryngeal Neoplasms / metabolism*
  • Magnetite Nanoparticles / chemistry*
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / chemistry
  • Nasopharyngeal Neoplasms / metabolism*
  • Neoplasm Transplantation
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Folate Receptors, GPI-Anchored
  • Magnetite Nanoparticles
  • Cisplatin