pH-Responsive Amylopectin Nanoparticles for On-Demand Glucose Production in Acidic Microenvironments

Glucose plays a crucial role in supplying energy to our bodies and fuels various cellular metabolic processes. An inadequate supply of glucose can disrupt these metabolic functions, potentially leading to health complications. To address these issues, we present a novel nanosystem designed to produce glucose in the slightly acidic environment found within the late endosomal/lysosomal compartment of cells. In this study, we employed amylopectin (AMY) polysaccharide as a substrate for the glucoamylase enzyme due to its biocompatible, biodegradable, and nontoxic nature. Through an acetal modification, amylopectin was transformed into an acid-sensitive hydrophobic material, acetalated amylopectin (AcAMY), enabling the formulation of particles and encapsulation of the glucoamylase with a high loading efficiency using a double emulsion method. These formulations showed a pH-dependent particle degradation and a controlled release of glucoamylase, facilitating the enzymatic hydrolysis of amylopectin to generate glucose. Moreover, this nanosystem exhibited efficient glucose production, reaching up to 80% glucose within 48 h under acidic conditions, in contrast to a maximum glucose production of 6% under physiological conditions. These findings demonstrate the particle's stability under the physiological environment of the bloodstream and highlight its ability to selectively produce glucose under acidic conditions. Cell viability results demonstrated that both enzyme-loaded and empty particles exhibit no toxicity, even at high particle concentrations, indicating excellent biocompatibility of this system. Consequently, this system shows great potential for effectively delivering glucose intracellularly to cells or tissues experiencing glucose deficiency.