Targeting CD133(+) laryngeal carcinoma cells with chemotherapeutic drugs and siRNA against ABCG2 mediated by thermo/pH-sensitive mesoporous silica nanoparticles

Tumour Biol. 2016 Feb;37(2):2209-17. doi: 10.1007/s13277-015-4007-9. Epub 2015 Sep 9.

Abstract

Mesoporous silica nanoparticles (MSNs) represent a new form of drug nanocarrier with thermo/pH-coupling sensitivity and site-specificity. CD133(+) Hep-2 laryngeal cancer cells are responsible for multidrug resistance due to elevated expression of ABCG2. Since positively charged nanoparticles could easily uptake nucleic acids, we examined the possibility of using this new drug delivery system to simultaneously deliver different chemotherapeutic drugs and siRNA targeting ABCG2. Our results demonstrated that both antitumor drugs and siRNA against ABCG2 were successfully delivered into CD133(+) cancer cells by loaded MSNs. Down-regulation of ABCG2 significantly enhanced the efficacy of chemotherapeutic drug-induced apoptosis in laryngeal carcinoma cells. Furthermore, the chemotherapeutic drug and siRNA loaded nanoparticles inhibited tumor growth in vivo in a laryngeal cancer mouse model.

Keywords: ABCG2; CD133+; Laryngeal carcinoma; siRNA nanoparticle.

MeSH terms

  • AC133 Antigen / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Cell Line, Tumor
  • Drug Carriers / pharmacology
  • Drug Delivery Systems / methods*
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Flow Cytometry
  • Gene Knockdown Techniques / methods
  • Humans
  • Laryngeal Neoplasms*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles*
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • RNA, Small Interfering / genetics*
  • Silicon Dioxide

Substances

  • ABCG2 protein, human
  • AC133 Antigen
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Antineoplastic Agents
  • Drug Carriers
  • Neoplasm Proteins
  • PROM1 protein, human
  • RNA, Small Interfering
  • Silicon Dioxide