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

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.

• Authors: Ahmad Fawzi Hussain, Harald Rune Krüger, Florian Kampmeier, Tim Weissbach, Kai Licha, Felix Kratz, Rainer Haag, Marcelo Calderón, Stefan Barth
• Journal: Biomacromolecules (Biomacromolecules) Vol. 14 Issue 8 Pg. 2510-20 (Aug 12 2013) ISSN: 1526-4602 [Electronic] United States
• PMID: 23782069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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