Self-Assembled Colloidal Gel Using Cell Membrane-Coated Nanosponges as Building Blocks

Abstract

<p class="first" id="P1">Colloidal gels that combine oppositely charged nanoparticles are increasingly leveraged for drug delivery and tissue engineering applications. Meanwhile, cell membrane-coated nanoparticles are becoming unique biomimetic nanomedicine for innovative therapeutics. Inspired by the remarkable potential of both platforms, herein we investigate the use of cell membrane-coated nanosponges as building blocks to form colloidal gel. Specifically, we prepare red blood cell membrane-coated nanoparticles (namely ‘nanosponges’, denoted ‘RBC-NPs’). In the presence of appropriate cationic nanoparticles, the nanosponges self-assemble to form a gel-like and cohesive complex (namely ‘nanosponge colloidal gel’, denoted ‘NC-gel’). When applied with an external shear force, the NC-gel shows shear-thinning behavior; however, upon removal of the external force, the cohesive property recovers. The NC-gel not only preserves the toxin neutralization capability of the nanosponges, but also prolongs their retention after subcutaneous injection into mouse tissues. In a mouse model of subcutaneous Group A <i>Streptococcus</i> (GAS) infection, the NC-gel shows significant antibacterial efficacy by markedly reducing skin lesion development. Overall, we demonstrate the successful use of cell membrane-coated nanoparticles as building blocks to formulate colloidal gel that entirely based on material self-assembly without chemical cross-linking. The new colloidal gel system is promising as an injectable formulation for therapeutic applications such as antivirulence treatment for local bacterial infections. </p>