Silk-based nanocomplexes with tumor-homing peptides for tumor-specific gene delivery

Macromol Biosci. 2012 Jan;12(1):75-82. doi: 10.1002/mabi.201100274. Epub 2011 Nov 3.

Abstract

Nanoscale complexes of recombinant silk molecules containing THPs with DNA are designed as less cytotoxic and highly target-specific gene carriers. Genetically engineered silk proteins containing poly(L-lysine) domains to interact with pDNA and the THP to bind to specific tumorigenic cells for target-specific pDNA delivery are prepared, followed by in vitro transfection into MDA-MB-435 melanoma cells, highly metastatic human breast tumor MDA-MB-231 cells, and non-tumorigenic MCF-10A breast epithelial cells. The silk/poly(L-lysine) block copolymer containing Lyp1 (ML-Lyp1) shows significant differences from silk/poly(L-lysine) block copolymer containing F3 (ML-F3) in cytotoxicity to MCF10A cells. ML-F3 is the most promising candidate for target delivery into tumorigenic cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Breast Neoplasms / therapy
  • Cell Survival
  • Drug Carriers / chemistry
  • Epithelial Cells / metabolism
  • Fibroins / chemistry
  • Fibroins / genetics*
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Humans
  • Melanoma / therapy
  • Microscopy, Electron, Scanning / methods
  • Models, Molecular
  • Molecular Sequence Data
  • Nanoconjugates / chemistry
  • Nanoconjugates / ultrastructure
  • Peptides / chemistry*
  • Plasmids / chemistry*
  • Polylysine / chemistry*
  • Protein Engineering / methods*
  • Recombinant Proteins / chemistry*
  • Recombinant Proteins / isolation & purification
  • Skin Neoplasms / therapy
  • Tumor Cells, Cultured

Substances

  • Drug Carriers
  • Nanoconjugates
  • Peptides
  • Recombinant Proteins
  • Polylysine
  • Fibroins