Nasopharyngeal cancer combination chemoradiation therapy based on folic acid modified, gefitinib and yttrium 90 co-loaded, core-shell structured lipid-polymer hybrid nanoparticles

Biomed Pharmacother. 2019 Jun:114:108820. doi: 10.1016/j.biopha.2019.108820. Epub 2019 Apr 2.

Abstract

Current treatment of advanced-stage nasopharyngeal carcinoma (NPC) is not satisfactory. Here, we developed a folic acid (FA) modified, gefitinib (GEF) and yttrium 90 (Y90) co-loaded, core-shell structured lipid-polymer hybrid nanoparticles (FA-GEF-Y90-LPNP). The size and zeta potential, drug release behavior, and uptake by tumor cells were investigated. The antitumor efficiency and toxicity of LPNP were evaluated in cancer cells and in tumor bearing mice. FA-GEF-Y90-LPNP with a mean size of 150 nm and zeta potential of -40 mV was able to enhance the accumulation in the NPC cells and exhibited the highest cytotoxicity. The AUC and T1/2 of FA-GEF-Y90-LPNP group was 217.62 ± 10.32 mg/L.h and 12.09 ± 0.43 h, respectively. FA-GEF-Y90-LPNP exhibited the best in vivo tumor inhibition ability, leading to a 221.2 ± 13.5 mm3 of tumor volume at day 21. FA-GEF-Y90-LPNP treatment resulted in almost no difference in the body weight. This may be the evidence that the systemic toxicity of FA-GEF-Y90-LPNP is low and may be used as safety system for the treatment of NPC.

Keywords: Antitumor ability; Chemoradiation; Co-delivery; Head and neck cancers; Nanomedicine.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemoradiotherapy / methods
  • Drug Carriers / chemistry
  • Folic Acid / pharmacology*
  • Gefitinib / pharmacology*
  • Humans
  • Lipids / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / radiotherapy*
  • Particle Size
  • Polymers / chemistry*
  • Yttrium Radioisotopes / pharmacology*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Lipids
  • Polymers
  • Yttrium Radioisotopes
  • Yttrium-90
  • Folic Acid
  • Gefitinib