Fluorinated DNA Micelles: Synthesis and Properties

Abstract

Creating new functional building blocks that expand the versatility of nanostructures depends on bottom-up self-assembly of amphiphilic biomolecules. Inspired by the unique physicochemical properties of hydrophobic perfluorocarbons, coupled with the powerful functions of nucleic acids, we herein report the synthesis of a series of diperfluorodecyl-DNA conjugates (PF-DNA) which can efficiently self-assemble into micelles in aqueous solution. On the basis of the micelle structure, both target binding affinity and enzymatic resistance of the DNA probe can be enhanced. In addition, based on the hydrophobic effect, the PF-DNA micelles (PFDM) can actively anchor onto the cell membrane, offering a promising tool for cell-surface engineering. Finally, the PFDM can enter cells, which is significant for designing carriers for intracellular delivery. The combined advantages of the DNA micelle structure and the unique physicochemical properties of perfluorocarbons make these PFDM promising for applications in bioimaging and biomedicine.

Enzymatic dephosphorylation-triggered self-assembly of DNA amphiphiles

“…As such, lipid tails act as a hydrophobic core and DNA act as a hydrophilic corona. [1][2][3] Because of their advantages of facile preparation, programmable design, small size (<100 nm) and biocompatibility, lipid-based DNA micelles show potential in the imaging of intracellular targets (mRNA and small molecules) and drug delivery. [4][5][6] To further improve their potential for better drug delivery and disease diagnosis, stimuli-responsive control of the change of morphology or assembly/disassembly of DNA micelles has attracted enormous attention in practical applications.…”

Chemically modified nucleic acid biopolymers used in biosensing

“…7). 75 Micelles formed by chain amphiphilic polymers have higher stability, and the critical micelle concentration values are significantly reduced. Thus, creating new hydrophobic building units enables the formation of amphiphilic biomolecules with different properties and expands the versatility of nanomicelles.…”

DNA Nanotechnology Enters Cell Membranes

“…Selected lipid‐oligonucleotide conjugates, exemplifying the variety of lipophilic residues that can be appended to DNA. Structures of DNA conjugated with, from top to bottom, cholesterol obtained via a 1,3‐dipolar Huisgen's cycloaddition between alkyne modified cholesterol and 5′‐azido‐5′‐deoxythymidine; a single hydrocarbon chain obtained via a 1,3‐dipolar Huisgen's reaction between alkyne modified C18 chain and 5′‐azido‐5′‐deoxythymidine; tocopherol obtained by covalent attachment to the 5′ end of the strand; a single fluorocarbon chain obtained via a Huisgen's reaction between 5′‐azide deoxythymidine and propargylated fluorocarbon chain; a PPO chain obtained via a PPO phosphoramidite during SPS; double hydrocarbon chains obtained via a reaction of stearoyl chloride with 1,3‐diamino‐2‐dydroxypropane; and double fluorocarbon chains obtained by a diperfluorodecyl phosphoramidite during SPS …”

“…The MBMFs showed efficient cell uptake, enhanced enzymatic stability, excellent target selectivity, and superior biocompatibility compared to pristine DNA. Diperfluorodecyl‐DNA conjugates allow further improvement of target binding affinity and enzymatic resistance by virtue of the physicochemical properties of fluorination . However, loss of integrity of micelles compromised the recognition ability of the aptamer when interacting with cells.…”