Herein we describe a nucleic acid functionalized nanocapsule in which nucleic acid ligands are assembled and disassembled in the presence of enzymes. The particles are fully degradable in response to esterases due to an embedded ester cross-linker in the particle's core. During synthesis the nanocapsules can be loaded with hydrophobic small molecules and post self-assembly undergo covalent cross-linking using copper catalyzed click chemistry. They can then be functionalized with thiolated DNA through stepwise thiolyne chemistry using UV light irradiation. Additionally, the capsule is compatible with enzyme mediated functionalization of a therapeutic mRNA-cleaving DNAzyme at the particle's surface. The resulting particle is highly stable, monodisperse in size, and maximizes the therapeutic potential of both the particles interior and exterior.

Herein, we describe the characterization of a novel self-assembling and intracellular disassembling nanomaterial for nucleic acid delivery and targeted gene knockdown. By using a recently developed nucleic acid nanocapsule (NAN) formed from surfactants and conjugated DNAzyme (DNz) ligands, it is shown that DNz-NAN can enable cellular uptake of the DNAzyme and result in 60 % knockdown of a target gene without the use of transfection agents. The DNAzyme also exhibits activity without chemical modification, which we attribute to the underlying nanocapsule design and release of hydrophobically modified nucleic acids as a result of enzymatically triggered disassembly of the NAN. Fluorescence-based experiments indicate that the surfactant-conjugated DNAzymes are better able to access a fluorescent mRNA target within a mock lipid bilayer system than the free DNAzyme, highlighting the advantage of the hydrophobic surfactant modification to the nucleic acid ligands. In vitro characterization of DNz-NAN's substrate-cleavage kinetics, stability in biological serum, and persistence of knockdown against a proinflammatory transcription factor, GATA-3, are presented.

Nanopores are emerging as a powerful tool for the investigation of nanoscale processes at the singlemolecule level. Here, we demonstrate the methionineselective synthetic diversification of α-hemolysin (α-HL) protein nanopores and their exploitation as a platform for investigating reaction mechanisms. A wide range of functionalities, including azides, alkynes, nucleotides, and single-stranded DNA, were incorporated into individual pores in a divergent fashion. The ion currents flowing through the modified pores were used to observe the trajectory of a range of azide−alkyne click reactions and revealed several short-lived intermediates in Cu(I)-catalyzed azide−alkyne [3 + 2] cycloadditions (CuAAC) at the singlemolecule level. Analysis of ion-current fluctuations enabled the populations of species involved in rapidly exchanging equilibria to be determined, facilitating the resolution of several transient intermediates in the CuAAC reaction mechanism. The versatile pore-modification chemistry offers a useful approach for enabling future physical organic investigations of reaction mechanisms at the single-molecule level.

Triazole-capped α-aminoisobutyric acid (Aib) octameric foldamers formed very active ion channels in phospholipid bilayers after the addition of copper(ii) chloride, with activity “turned off” by copper(ii) extraction.

Nanopore technology has established itself as a powerful tool for single-molecule studies. By analysing changes in the ion current flowing through a single transmembrane channel, a wealth of molecular information...