Spherically Directed Synthesis and Enhanced Cellular Internalization of Metal-Crosslinked DNA Micelles

Abstract

We describe a facile and universal method that uses spherically directed reduction of metal ions for in situ crosslinking of DNA micelles. By combining characterization results and simulation algorithms, we achieved accurate structural profiling of DNA micelles for the first time. The metal-crosslinked DNA micelle, or MDM, combines the facile preparation and dense ligand distribution of a DNA micelle with the physical properties of DNA-metal-particle conjugates. As a result of the metal crosslink, the internalization efficiency of MDM is much greater than that of DNA micelles. HIGHLIGHTS Spherically directed reduction is a universal method for DNA micelle crosslinkingThe detailed structural profile of DNA micelles was determinedThe internalization efficiency of MDM is greatly enhanced compared with DNA micelles Double-stranded DNA with two cholesterol modifications can also be used to form MDMs Lyu et al., Chem 5,[913][914][915][916][917][918][919][920][921][922][923][924][925][926][927][928] April 11, 2019 ª SUMMARY Using spherically directed reduction of metal ions, a facile and universal method for in situ crosslinking of DNA micelles is described. By incorporating a series of specific template domains into lipid-DNA monomers, copper-, silver-, and goldcrosslinked DNA micelles are formed. By combining characterization results and simulation algorithms, accurate structural profiling of DNA micelles is achieved for the first time. The prepared metal-crosslinked DNA micelles show obvious merits, including one-step formation of core structure and ligand corona, facile size tunability, monodispersity, stability against salt-induced aggregation, high utilization of DNA ligand, mild synthesis conditions, and less time consumption and better internalization. Based on our spherically directed synthesis, metalcrosslinked DNA micelle flares were further prepared for effective intracellular imaging by integrating an aptamer-toehold strategy. In addition, we extended the strategy to cholesterol-based double-stranded DNA micelles, giving strong evidence that our method is not only universal but also flexible.

Chemically modified nucleic acid biopolymers used in biosensing

“…83,84 Lyu et al designed a method for DNA micelle crosslinking in situ with the assistance of metal ions. 85 The monomer that makes up the micelle is formed by the covalent attachment of a single stranded DNA and a hydrophobic diacyl lipid. Specifically, the monomer consists of three parts, the most important of which is the part that acts as a template chain (Fig.…”

Cytomembrane‐Mediated Transport of Metal Ions with Biological Specificity

“…Nevertheless, exotic materials would inevitably induce unwanted immune response, and up to date, the fate of the majority of man‐made polymers remains ambiguous yet . This dilemma inspires researchers to embark on the transport of metal ions using biomacromolecules coming from life systems, such as the recently highlighted proteins and genes . Unfortunately, these biomacromolecules fail to find their way to the targeted sites when in vivo administrated, leading to significant concerns, for example, systematic toxicity and drug tolerance of patients .…”

Lipid–oligonucleotide conjugates for bioapplications

“…In terms of LONs, fast micelle formation was also able to prevent degradation by nuclease, possibly resulting from the steric hindrance of the DNA corona. Subsequent studies in the Tan group further improved the physical and biological stability of DNA–lipid micelles [ 46 – 48 ]. Our most recent study reported the introduction of a methacrylamide unit between the DNA and lipid segments, which served to cross link the amphiphiles after self-assembly via photoinduced polymerization (Fig.…”