Expanding the Chemical Repertoire of DNA Nanomaterials Generated by Rolling Circle Amplification

Rolling circle amplification (RCA) is a powerful tool for the construction of DNA nanomaterials such as hydrogels, high-performance scaffolds and DNA nanoflowers (DNFs), hybrid materials formed of DNA and magnesium pyrophosphate. Such DNA nanomaterials have great potential in therapeutics, imaging, protein immobilisation, and drug delivery, yet limited chemistry is available to expand their functionality. Here, we present an orthogonal strategy to produce densely modified RCA products and DNFs. We show that it is possible to selectively functionalise the DNA component of these materials, their protein cargo, or both, thereby greatly expanding the chemical repertoire available to these systems. We then use this methodology to construct DNFs bearing multiple surface aptamers capable of binding to cancer cells that overexpress the HER2 oncobiomarker, demonstrating the therapeutic and diagnostic potential of this chemistry.