Ligand-mediated targeting of nanocarriers to tumors is an attractive strategy for increasing the efficiency of chemotherapies. Sialylated glycans represent a propitious target as they are broadly overexpressed in tumor cells. Because phenylboronic acid (PBA) can selectively recognize sialic acid (SA), herein, we developed PBA-installed micellar nanocarriers incorporating the parent complex of the anticancer drug oxaliplatin, for targeting sialylated epitopes overexpressed on cancer cells. Following PBA-installation, the micelles showed high affinity for SA, as confirmed by fluorescence spectroscopy even at intratumoral pH conditions, i.e., pH 6.5, improving their cellular recognition and uptake and enhancing their in vitro cytotoxicity against B16F10 murine melanoma cells. In vivo, PBA-installed micelles effectively reduced the growth rate of both orthotopic and lung metastasis models of melanoma, suggesting the potential of PBA-installed nanocarriers for enhanced tumor targeting.

Protein‐free: A hydrogel containing phenylboronate was optimized so as to undergo rapid glucose‐dependent changes in the state of hydration under physiological aqueous conditions. A localized dehydration of the gel surface to form a “skin layer” enabled control of the release of insulin from the gel. This dehydration is induced by fluctuations in the glucose concentration in the range between normo‐ and hyperglycemia.

A question of concentration: The condensation of ethyleneurea and formaldehyde can be controlled perfectly by the HCl concentration to provide either a hemicucurbit[6]uril 1, which functions as a host, or hemicucurbit[12]uril 2, which acts as a gelating agent, in yields of 94 and 93 %, respectively.

Therapeutics based on small interfering RNA (siRNA) offer an attractive clinical option because of its ability to silence genes in a highly sequence-specific manner.[1] A key challenge lies in developing a delivery system that helps protect the siRNAs from endogenous RNase degradation while allowing for controlled pharmacokinetics. One promising approach is a formulation of polyion complex (PIC) micelles that spontaneously form in an aqueous environment simply through electrostatic interactions between the anionic siRNA and cationic polymers.[2] With versatile designs of the counterpart cationic polymers, representative poly(ethylene glycol) based block co-polymers, many creative PIC-based strategies have emerged, some of which have shown encouraging in vitro gene silencing abilities. [3][4][5] However, in general, these PIC-based carriers suffer from instability under physiological conditions, primarily because of the relatively short chain length of the siRNA, that is 20-25 nucleotides, which results in poor thermodynamic stability. Therefore, stabilization of the PIC-based carriers so that programmed destabilization upon arrival at the site of intracellular targets (to release siRNA) has been of interest. Current efforts have focused on either one or combinations of the following three representative approaches: covalent conjugation of siRNAs to a homing polymer, [3,[6][7][8] introduction of hydrophobic moieties to reinforce the core-aggregation, [9][10][11] and crosslinking the core aggregate by disulfide bridging. [5,12] As such, the combination of these approaches often results in a highly complex structure and method of preparation.Herein, we describe a sophisticated solution that can remarkably simplify the synthesis of PICs. It uses a phenylboronate functionality, which incorporates all of the aforementioned methods of stabilization (Scheme 1) while maintaining a wide window of control for environmental sensitivity. Phenylboronic acid (PBA) is a synthetic molecule capable of forming reversible covalent esters with 1,2-or 1,3-cis-diols including on a ribose ring, [13][14][15] a structure which is present at the 3' end of RNAs and several kinds of ribonucleotides. Because of this property, PBA has historically been used as a ligand for RNA in affinity chromatography.[16] Therefore, this binding property offers a facile route for chemical conjugation of siRNAs to the pendant PBA groups. Once electrostatically condensed into the PIC, the chances of equilibrium binding are increased, in which intermolecular cross-links could also form because of the bis-bidentate ribose arrangement at the 3' end of the double-stranded siRNA, thereby further stabilizing the complex. Furthermore, PBA is unique in that it undergoes a dramatic inversion in its level of hydrophobicity depending on the degree of acid disassociation; [17] it is strongly hydrophobic when uncharged but it becomes hydrophilic when negatively charged at pH values above its pK a . As shown in Figure 1, the binding between PBA and siRNAs is essentially a ...

Alternations of sialic acid (SA) content on cell surface glycan chains have been implicated in numerous normal and pathological processes including developments, differentiations, and tumor metastasis. Overexpressions of SA have been implicated in the malignant and metastatic phenotypes for many different types of cancers, while decreased SA expression has also been identified in erythrocytes of diabetic mellitus. Techniques to conveniently monitor cell surface SA would therefore have great relevance to cytology. Preexisting methodologies to quantify SA, however, involve multiple enzymatic, dye-labeling, and lethal procedures, which are costly and time-consuming. Here we developed a potentiometric SA detection using a phenylboronic acid (PBA) compound integrated into the form of a self-assembled monolayer (SAM) onto a field effect transistor (FET) extended gold gate electrode. Due to selective binding between undisassociated PBA and SA at pH 7.4 among other glycan chain constituent monosaccharides, we found that carboxyl anions of SA were exclusively detectable as the change in threshold voltage (V(T)) of the PBA-modified FET. The technique was applied to analyses of altered SA expressions on rabbit erythrocyte as a model for diabetes. Comparative SA expression analyses for each healthy and diseased model revealed that the disease could be feasibly diagnosed simply by placing the known-count cell suspensions onto the device without any labeling and enzymatic procedures. Such a technique may also provide a quantitative adjunct to histological evaluation of tumor malignancy and metastatic potential during intra- and postoperative diagnoses. Also advantageously, a technique herein described is all within a CMOS (Complementary Metal Oxide Semiconductor) compatible format thus promising for highly efficient and low cost manufacturing with readiness of downsizing and integration by virtue of advanced semiconductor processing technologies.

In a world without labels…︁ A self‐assembled phenylboronic acid monolayer on the surface of a gold electrode enabled the potentiometric detection of cell‐membrane sialic acid (SA; see diagram) and differentiation of healthy pneumocytes from metastatic melanoma cells on the basis of altered SA expression. This approach to the diagnosis of tumoral malignancy or the degree of metastasis holds promise for label‐free, noninvasive, real‐time cytology.

Here described is a phenylboronic acid (PBA) based glucose-responsive hydrogel operating under physiological pH and temperature, a material potentially applicable to a totally synthetic smart insulin delivery system to treat diabetes.

A synthetic polymer gel–based insulin delivery device provides an artificial pancreas–like function in healthy and diabetic mice.