The metal crosslinked DNA micelle

The metal-crosslinked DNA micelle, or MDM, is an interesting DNA-micelle/DNA-nanoparticle conjugate that combines the facile preparation and dense ligand distribution of a DNA micelle with the physical properties of the widely used spherical nucleic acids (SNAs) reported by Mirkin and coworkers. Compared with the typical SNA preparation approach, which involves synthesizing gold nanoparticles (AuNP) in boiling solution and modification of DNA ligand using the well-established Au-S chemistry, our spherically directed strategy is simply a one-pot reaction at room temperature and much more universal for different kinds of metals. In addition, the extremely low CMC of DNA VU 591 hydrochloride australia enables highly efficient micelle formation in solution and, together with the templated-reduction procedure, permits much higher utilization efficiency of DNA strands than the regular DNA-particle conjugation method. Because of the metal crosslink, the internalization efficiency of MDM is much greater than that of DNA micelles. On the basis of all the above properties, we further prepared a metal-crosslinked DNA micelle flare (MDMF) for intracellular ATP imaging by adapting an aptamer-toehold-based strategy. Benefitting from the excellent biocompatibility of MDMs, MDMFs showed negligible cytotoxicity and effective self-delivery as an intracellular sensing platform, demonstrating the huge potential of MDMs in biological applications. Apart from lipid-based ssDNA micelles, by using double-stranded DNA (dsDNA) with two cholesterol modifications to form a micelle, we prove that these dsDNA micelles can also be used to form MDMs by designing a specific dsDNA template domain, which is an extension of our strategy and strong evidence of the flexibility of our method.
Results
Discussion In summary, using a spherically directed synthesis of metal-crosslinked DNA micelles, as well as a series of simulation algorithms, we succeeded in acquiring a detailed structural profile of a DNA micelle. The programmability of DNA strands and the selectivity of the DNA template permitted the effective crosslinking of DNA micelles by three kinds of metal ions, including copper, silver, and gold, generating a hollow or solid core structure. This strategy gives a facile approach for crosslinking DNA micelles, as well as a universal and time-saving method for preparing DNA-metal nanoparticle conjugates. The size of the metal core can be controlled by designing the length or sequence of the template domain, which makes it a flexible parameter in programmable synthesis. Compared with the typical SNA preparation approach, which consists of synthesizing AuNPs in boiling solution and modification of DNA ligand via Au-S chemistry, our spherically directed strategy is simply a one-pot reaction at room temperature and is much more universal for different kinds of metals. Unlike DNA micelles, which fuse with the cell membrane, MDMs were found to have good cellular internalization. Furthermore, by integrating an aptamer-toehold-mediated ATP detection strategy, MDMFs were prepared for effective intracellular imaging, which demonstrated the feasibility of MDMs in biological applications. In addition, this is the first report of micelle formation by cholesterol-modified dsDNA instead of the usual single-stranded cholesterol-DNA. These results not only extend the preparation methods of metal-crosslinked DNA micelles but also inspire numerous potential DNA micelle applications.