Targeted delivery of dendritic polyglycerol-doxorubicin conjugates by scFv-SNAP fusion protein suppresses EGFR+ cancer cell growth

Biomacromolecules. 2013 Aug 12;14(8):2510-20. doi: 10.1021/bm400410e. Epub 2013 Jul 3.

Abstract

Development of effective polymer-based nanocarriers for the successful application in cancer therapy still remains a great challenge in current research. In the present study we present a dendritic polyglycerol-based multifunctional drug immunoconjugate that specifically targets and kills cancer cell lines expressing epidermal growth factor receptor (EGFR). The nanocarrier was provided with a dendritic core as a multifunctional anchoring point, doxorubicin (Doxo) coupled through a pH-sensitive linker, a fluorescence marker, poly(ethylene glycol), as solubilizing and shielding moiety, and a scFv antibody conjugated through the SNAP-Tag technology. The study provides the proof of principle that SNAP-tag technology can be used to generate drug-carrying nanoparticles efficiently modified with single-chain antibodies to specifically target and destroy cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • CHO Cells
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cricetinae
  • Cricetulus
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems
  • Drug Screening Assays, Antitumor
  • Guanine / analogs & derivatives
  • Guanine / chemistry
  • Humans
  • O(6)-Methylguanine-DNA Methyltransferase / chemistry
  • Protein Binding
  • Recombinant Fusion Proteins / chemistry
  • Single-Chain Antibodies / chemistry

Substances

  • Antineoplastic Agents
  • Dendrimers
  • Recombinant Fusion Proteins
  • Single-Chain Antibodies
  • O(6)-benzylguanine
  • Guanine
  • Doxorubicin
  • O(6)-Methylguanine-DNA Methyltransferase