Redox-Responsive Nanogels for Precision Protein Delivery
Rupali Dabas, Nazila Kamaly
Abstract
• Nanogel carriers can protect proteins from degradation and provide controlled release. • This work developed redox-responsive nanogels for targeted intracellular protein delivery. • Redox-responsive nanogels were successfully developed for targeted intracellular protein delivery. • Precision protein release inside cells was achieved via incorporation of disulfide crosslinkers. • These nanocarriers have promising applications for enhanced efficacy of protein therapeutics. Redox-responsive drug carriers present a therapeutically viable delivery platform owing to their ability to leverage the intracellular redox environment. In this work, we describe a facile, one-pot aqueous-based synthetic methodology for encapsulating sensitive biological payloads within redox-responsive crosslinked nanogels. We systematically evaluate the impact of various disulphide-based crosslinkers on the morphology, stability, encapsulation and loading capacities of these nanogels. In vitro assessments were conducted to elucidate the ease of delivery of functional protein payloads, using fluorescently-labelled bovine serum albumin and the enzyme, paraoxonase-1. The nanogels demonstrate promising delivery efficiencies with minimal cytotoxicity in vitro . The simplicity of their synthesis, along with the precise control achieved in nanogel degradation and payload release kinetics, not only enriches our understanding of redox-responsive nanosystems but also underscores their potential to catalyze transformative advancements in intracellular protein delivery.