Angew. Chem. Int. Ed.http://doi.org/fz5qc7 (2012)

Credit: © 2012 WILEY

The transmembrane G-protein receptor CXCR4 and its ligand CXCL12 are known to be involved in the metastasis of cancer cells to other sites in the body; therefore, blocking this interaction is an important strategy in cancer therapy. Small-molecule inhibitors of CXCR4, for example, the bicyclam derivative AMD3100, have shown antagonistic behaviour and antimetastatic activity in some cancers. Now, David Oupický and colleagues have synthesized a polycationic biodegradable system incorporating AMD3100 and plasmid DNA, which demonstrates both CXCR4 antagonism and gene delivery to bone cancer cells. These polycation–DNA species, or polyplexes, show the concurrent ability to inhibit cancer cell invasion, deliver plasmid DNA and mediate transfection. The polyplexes are made by the Michael addition polymerization of AMD3100 with a disulphide-containing bisacrylamide, followed by addition of plasmid DNA. Although the polyplexes do not need to be internalized to show CXCR4 antagonism, this is required for the gene delivery step. Oupický and colleagues found that a different uptake pathway other than the CXCR4 receptor is used for polyplex transfection and delivery.