Collagen mimetic peptide engineered M13 bacteriophage for collagen targeting and imaging in cancer

Biomaterials. 2014 Nov;35(33):9236-45. doi: 10.1016/j.biomaterials.2014.07.044. Epub 2014 Aug 10.

Abstract

Collagens are over-expressed in various human cancers and subsequently degraded and denatured by proteolytic enzymes, thus making them a target for diagnostics and therapeutics. Genetically engineered bacteriophage (phage) is a promising candidate for the development of imaging or therapeutic materials for cancer collagen targeting due to its promising structural features. We genetically engineered M13 phages with two functional peptides, collagen mimetic peptide and streptavidin binding peptide, on their minor and major coat proteins, respectively. The resulting engineered phage functions as a therapeutic or imaging material to target degraded and denatured collagens in cancerous tissues. We demonstrated that the engineered phages are able to target and label abnormal collagens expressed on A549 human lung adenocarcinoma cells after the conjugation with streptavidin-linked fluorescent agents. Our engineered collagen binding phage could be a useful platform for abnormal collagen imaging and drug delivery in various collagen-related diseases.

Keywords: Bacteriophage; Cancer; Collagen; Imaging; Targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma
  • Adenocarcinoma of Lung
  • Bacteriophage M13 / genetics*
  • Biomimetics
  • Capsid Proteins / chemistry
  • Capsid Proteins / genetics
  • Cell Line, Tumor
  • Collagen / chemistry
  • Collagen / genetics*
  • Diagnostic Imaging / methods*
  • Drug Delivery Systems*
  • Fluorescent Dyes
  • Humans
  • Lung Neoplasms
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Neoplasms / therapy
  • Peptides / chemistry
  • Peptides / genetics
  • Protein Binding
  • Streptavidin / chemistry
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Capsid Proteins
  • Fluorescent Dyes
  • Peptides
  • Transforming Growth Factor beta1
  • Collagen
  • Streptavidin
  • Matrix Metalloproteinases