Biased Borate Esterification during Nucleoside Phosphorylase-Catalyzed Reactions: Apparent Equilibrium Shifts and Kinetic Implications.

Biocatalytic nucleoside (trans-)glycosylations catalyzed by nucleoside phosphorylases have evolved into a practical and convenient approach to the preparation of modified nucleosides, which are important pharmaceuticals for the treatment of various cancers and viral infections. However, the obtained yields in these reactions are generally determined exclusively by the innate thermodynamic properties of the nucleosides involved, hampering the biocatalytic access to many sought-after target nucleosides. We herein report an additional means for reaction engineering of these systems. We show how apparent equilibrium shifts in phosphorolysis and glycosylation reactions can be effected through entropically driven, biased esterification of nucleosides and ribosyl phosphates with inorganic borate. Our multifaceted analysis further describes the kinetic implications of this in situ reactant esterification for a model phosphorylase.

Guanosine-based Hydrogel Integrating Photothermal Effect of PDA-AuNPs through Dynamic Borate Bond for Photothermal Therapy of Cancer.

Photothermal therapy (PTT) has drawn extensive attention owing to its noninvasive and great tissue penetration depth. However, the physical encapsulation of photothermal agents may lead to their rapid release. Dual-functional hydrogel systems that integrate functions and carriers can potentially solve this problem. In this work, we successfully developed a dual-functional guanosine(G)-based hydrogel integrating the photothermal effect and localized delivery by introducing dynamic borate ester utilizing the photothermal property of PDA-AuNPs and the self-assembly ability of G. Both in vitro and in vivo results confirmed that the GBPA hydrogel not only exhibited excellent photothermal toxicity, stability, injectability, and biocompatibility, but also possessed high photothermal antitumor activity. These results suggested that the GBPA hydrogel could be used as a dual-functional hydrogel integrating photothermal effect and localized delivery in one system, which would possibly provide a new opportunity for the design of new dual-functional hydrogels for highly efficient cancer therapy.

Engineered borate ester conjugated protein-polymer nanoconjugates for pH-responsive drug delivery.

To improve the clinical efficiency of cytotoxic anticancer drugs e.g. doxorubicin (DOX), reduce the severe off-target side effects, and allow the more biocompatible and biodegradable drug penetration into tumor cells, our research efforts developed a new DOX-conjugated protein polymer nanoconjugates (PPNCs) prodrugs delivery system. Briefly, DOX was conjugated to bovine serum albumin (BSA) and the complex was treated with lactobionic acid (LA) as well as folic acid (FA) to enhance drug endocytosis and targeting selectivity. Such functionalized BSA could be conjugated with a designed phenylboronic acid functionalized poly(N-isopropylacrylamide) (PNIPAAm) via forming a pH-sensitive borate ester bond to give the functionalized PPNCs prodrugs. The potential of the PPNCs prodrugs on tumor cells therapy was systematically evaluated in dose/time-dependent effects. In vitro results showed a rapid accumulation of the prodrugs into the MDA-MB-231 tumor cell during the first 30 min and reached maximum at 24 h. Moreover, the cell-killing effect was observed quickly after 4 h incubation with an IC50 of 0.5 mg/mL (≈4 µM/L). In general, given the efficient pH-dependent DOX release of these constructed nanoconjugates, it is anticipated to contribute a potential delivery strategy for cancer therapy.

Magnetic Relaxation Switch Detecting Boric Acid or Borate Ester through One-Pot Synthesized Poly(vinyl alcohol) Functionalized Nanomagnetic Iron Oxide.

We developed a highly efficient magnetic relaxation switch (MRS) system based on poly(vinyl alcohol) functionalized nanomagnetic iron oxide (PVA@NMIO) particles for the detection of boric acid or borate ester (BA/BE). It was found that the addition of BA/BE induced the aggregation of PVA@NMIO particles, resulting in a measurable change in the T2 relaxation time in magnetic resonance measurements. The main mechanism was proposed that the electron-deficient boron atoms of BA/BE caused the aggregation of PVA@NMIO particles through covalent binding to the hydroxyl groups of PVA. This novel detection system displayed excellent selectivity, high sensitivity, and rapid detection for BA/BE. Thus, this system may provide a great application prospect for detection of BA/BE.