New generation of electrochemical immunoassay based on polymeric nanoparticles for early detection of breast cancer

Int J Nanomedicine. 2017 Apr 13:12:3037-3047. doi: 10.2147/IJN.S127086. eCollection 2017.

Abstract

Screening and early diagnosis are the key factors for the reduction of mortality rate and treatment cost of cancer. Therefore, sensitive and selective methods that can reveal the low abundance of cancer biomarkers in a biological sample are always desired. Here, we report the development of a novel electrochemical biosensor for early detection of breast cancer by using bioconjugated self-assembled pH-responsive polymeric micelles. The micelles were loaded with ferrocene molecules as "tracers" to specifically target cell surface-associated epithelial mucin (MUC1), a biomarker for breast and other solid carcinoma. The synthesis of target-specific, ferrocene-loaded polymeric micelles was confirmed, and the resulting sensor was capable of detecting the presence of MUC1 in a sample containing about 10 cells/mL. Such a high sensitivity was achieved by maximizing the loading capacity of ferrocene inside the polymeric micelles. Every single event of binding between the antibody and antigen was represented by the signal of hundreds of thousands of ferrocene molecules that were released from the polymeric micelles. This resulted in a significant increase in the intensity of the ferrocene signal detected by cyclic voltammetry.

Keywords: biosensors; breast cancer biomarkers; electrochemical immunoassay; polymeric nanoparticles.

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Biosensing Techniques / instrumentation
  • Biosensing Techniques / methods*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Electrochemical Techniques / instrumentation
  • Electrochemical Techniques / methods
  • Female
  • Ferrous Compounds / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Immunoassay / instrumentation
  • Immunoassay / methods*
  • Metallocenes
  • Mice
  • Micelles
  • Mucin-1 / analysis*
  • Mucin-1 / immunology
  • Mucin-1 / metabolism
  • Nanoparticles / chemistry
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polymers / chemical synthesis
  • Polymers / chemistry
  • Polymethacrylic Acids / chemical synthesis
  • Polymethacrylic Acids / chemistry
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Ferrous Compounds
  • MUC1 protein, human
  • Metallocenes
  • Micelles
  • Mucin-1
  • Polymers
  • Polymethacrylic Acids
  • poly(ethylene glycol-b-trimethylsilyl methacrylate)
  • Polyethylene Glycols
  • ferrocene