Boronate based metal-free platform for diphosphate-specific molecular recognitions.

A reversible boronate-diol interaction provides a versatile synthetic platform for molecular recognitions whose binding specificity can be molecularly tailored. We found that boronate derivatives with relatively strong acidity generally undergo a diphosphate-specific recognition among other phosphates under weakly acidic pH conditions, a feature relevant to DNA sequencing. (11)B and (31)P NMR studies identified "tetrahedral boronate and divalent diphosphate" as a pair responsible for forming a 1:1 stoichiometric complex, which manifests as a unique pH-dependent stability.

Phenylboronic acids-based diagnostic and therapeutic applications.

Phenylboronic acid (PBA) derivatives are known to form reversible complexes with polyols, including sugars. This unique chemistry has provided many useful molecular bases for analytical and therapeutic applications. This mini-review highlights some new aspects of related research efforts with a special focus on the interaction with sialic acid as a new class of molecular targets and other PBA-based strategies for drug delivery applications.

Thiolated 2-methacryloyloxyethyl phosphorylcholine for an antifouling biosensor platform.

We developed a new building block for a protein- and cell-repellant self-assembled monolayer (SAM) from 2-methacryloyloxyethyl phosphorylcholine (MPC) via a simple Michael-type addition to one mercapto group in alkanedithiol. The thiolated MPC can enable functionalization of a noble metal electrode to minimize noise signal in biosensing.

Dual environment-responsive polyplex carriers for enhanced intracellular delivery of plasmid DNA.

In this study, we describe a multifunctional, nontoxic delivery vehicle with dual-environment sensitivity to deliver plasmid DNA (pDNA) into the cytoplasm of cells. This delivery vehicle was designed to be destabilized by reduction of disulfide cross-links in the intracellular environment and also to contain pH-sensitive membrane-destabilizing activity in acidic late endosomal/lysosomal compartments to allow escape of pDNA into the cell cytoplasm. Polyion complex formation was used to form ternary polyplexes using ionic polymers containing specific chemistries to achieve functional demands.

pDNA/poly(L-lysine) Polyplexes Functionalized with a pH-Sensitive Charge-Conversional Poly(aspartamide) Derivative for Controlled Gene Delivery to Human Umbilical Vein Endothelial Cells.

An efficient endosome-escaping function was integrated into the polyplex of plasmid DNA (pDNA) with poly(L-lysine) (PLys) to improve its gene transfection efficiency through electrostatic coating with charge-conversional polymer (CCP). CCP showed charge-conversional function responding to endosomal pH, leading to the release of pDNA/PLys polyplex into the cytoplasm. The cells took up the intact CCP-integrated ternary polyplex, which exerted appreciably higher transfection efficiency with lower cytotoxicity than pDNA/PLys polyplex against human umbilical vein endothelial cells (HUVECs).

Polyplex micelles prepared from ω-cholesteryl PEG-polycation block copolymers for systemic gene delivery.

Polyplex micelles formed with plasmid DNA (pDNA) and poly(ethylene glycol) (PEG)-block-poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)] exhibit effective endosomal escaping properties based on di-protonation of diamine side chains with decreasing pH, which improves their transfection efficiency and thus are promising candidates for local in vivo gene transfer. Here, PEG-PAsp(DET) polyplex micelles were further improved as in vivo systemic vectors by introduction of cholesterol (Chole) into the ω-terminus of PEG-PAsp(DET) to obtain PEG-PAsp(DET)-Chole. Introduction of the cholesterol resulted in enhanced association of block copolymers with pDNA, which led to increased stability in proteinous medium and also in the blood stream after systemic injection compared to PEG-PAsp(DET) micelles.