Abstract
We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Herein, we utilize boronate cis-diol interactions to develop a glucose-responsive submicron particle (SMP) system. The stability of the boronate interaction at a physiological pH was achieved by copolymerization of dimethyl aminoethyl methacrylate (DMAEMA) with acrylamidophenylboronic acid (AAPBA) and the formation of a complex with polyvinylalcohol (PVA) which is governed by cis-diol interactions. The shift in hydrodynamic diameter of SMPs was observed and correlated with increasing glucose concentrations at a physiological pH. Optimal transfection was observed for a 5 µg dose of the gaussia luciferase reporter gene in NIH3T3 cells without any adverse effect on cellular viability. The destabilization of the AAPBA–PVA complex by interacting with glucose allowed the release of encapsulated bovine serum albumin (BSA) in a glucose-responsive manner. In total, 95% of BSA was released from SMPs at a 50 mM glucose concentration after 72 h. A two-fold increase in transfection was observed in 50 mM glucose compared to that of 10 mM glucose.
Highlights
We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material
Glucose-responsive delivery systems are widely preferred stimulus-responsive delivery systems based on Glucose oxidase enzyme (GOx), glucose binding proteins (GBPs), and phenylboronic acid (PBA) [6]
One-pot synthesis of acrylamidophenylboronic acid (AAPBA)–PVA complex with dimethyl aminoethyl methacrylate (DMAEMA) stabilization was performed in this study
Summary
We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Low transfection is one of the main barriers associated with nonviral gene carriers [1,2,3] This challenge can be solved by the use of a stimulus-responsive delivery system [4]. Glucose-responsive delivery systems are widely preferred stimulus-responsive delivery systems based on Glucose oxidase enzyme (GOx), glucose binding proteins (GBPs), and phenylboronic acid (PBA) [6]. The use of these glucose oxidase-based systems is minimal, as enzyme activity can be reduced over time [7].
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