Abstract
The CXCR4 chemokine receptor is an important biomolecular target in cancer diagnostics and therapeutics. In a new multivalent approach, iron oxide nanoparticles were conjugated with multiple binding units of a low affinity azamacrocylic CXCR4 antagonist. The silica coated nanostructure has good suspension stability, a mode size of 72 nm and high affinity for CXCR4, showing >98% inhibition of anti-CXCR4 mAb binding in a receptor binding competition assay on Jurkat cells.
Highlights
The CXCR4 chemokine receptor is an important biomolecular target in cancer diagnostics and therapeutics
Over the last ten years, our work has developed rigidly constrained azamacrocycle metal complexes as CXCR4 antagonists, building on the structure activity relationship of FDA approved drug AMD3100.10 The new compounds have fixed configurations, increased potency and longer receptor residence time, with affinities for the CXCR4 chemokine receptor from sub-nanomolar to several micromolar, e.g. 1–3.7,11–15 This offers an ideal platform to optimise nanoparticle (NP) affinity for this receptor target in cancer, see Fig. 1.13 The first step is to develop an attachment method and to validate the multivalent binding approach.[16,17]
Chittasupho et al using cellulose NPs coated with poly lactic-co-glycolic acid (PLGA) for drug delivery, targeting CXCR4 with the LFC131 peptide.[20]
Summary
The CXCR4 chemokine receptor is an important biomolecular target in cancer diagnostics and therapeutics. In a new multivalent approach, iron oxide nanoparticles were conjugated with multiple binding units of a low affinity azamacrocylic CXCR4 antagonist.
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