Human papilloma virus DNA-biomarker analysis for cervical cancer: Signal enhancement by gold nanoparticle-coupled tetravalent streptavidin-biotin strategy

Int J Biol Macromol. 2019 Aug 1:134:354-360. doi: 10.1016/j.ijbiomac.2019.05.044. Epub 2019 May 10.

Abstract

Human papillomavirus (HPV) is a double-standard DNA virus, as well as the source of infection to the mucous membrane. It is a sexually transmitted disease that brings the changes in the cervix cells. Oncogenes, E6 and E7 play a pivotal role in the HPV infection. Identifying these genes to detect HPV strains, especially a prevalent HPV16 strain, will bring a great impact. Among different sensing strategies for pathogens, the dielectric electrochemical biosensor shows the potential due to its higher sensitivity. In this research, HPV16-E7 DNA sequence was detected on the carbodiimidazole-modified interdigitated electrode (IDE) surface with the detection limit of 1 fM. To enhance the sensitivity, the target sequence was conjugated on gold nanoparticle (GNP) and attained detection to the level of 10 aM. This produced ~100 folds improvement in detecting HPV16-E7 gene and 4 folds increment in the current flow. The stability of HPV16-E7 DNA sequences on GNP was verified by the salt-induced GNP aggregation. The current system has shown the higher specificity by comparing against non-complementary and triple-mismatched DNA sequences of HPV16-E7. This demonstration in detecting HPV16-E7 using dielectric IDE sensing system with a higher sensitivity can be recommended for detecting a wide range of disease-causing DNA-markers.

Keywords: Cervical cancer; DNA-sensor; Gold nanoparticle; Human papillomavirus; Interdigitated electrode.

MeSH terms

  • Base Sequence
  • Biomarkers / metabolism
  • Biosensing Techniques / methods*
  • Biotin / chemistry*
  • DNA, Viral / analysis*
  • DNA, Viral / genetics
  • Female
  • Gold / chemistry*
  • Humans
  • Limit of Detection
  • Metal Nanoparticles / chemistry
  • Papillomavirus E7 Proteins / genetics*
  • Streptavidin / chemistry*
  • Uterine Cervical Neoplasms / virology*

Substances

  • Biomarkers
  • DNA, Viral
  • Papillomavirus E7 Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • Biotin
  • Gold
  • Streptavidin