Dual-Reactive Nanogels for Orthogonal Functionalization of Hydrophilic Shell and Amphiphilic Network

ALEXANDRA GRUBER; LUCILA NAVARRO; DANIEL KLINGER

SOFT MATTER

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2022

1744-683X

Amphiphilic nanogels areemerging as new nanocarriers that combine a soft, water-swollen hydrogel matrixwith internal hydrophobic domains. While these domains allow the encapsulationof hydrophobic cargoes, the amphiphilic nanogel surface can reduce colloidalstability and/or limit biological half-life. Therefore, a functionalhydrophilic shell is needed to shield the amphiphilic structure and tune interactionswith biological systems. Thus, multi-functional amphiphilic nanogels shouldcontain a stimuli-responsive network and a hydrophilic shell that allowsfurther functionalization. To address these requirements, we used an alkyne end-functionalized block copolymersurfactant for the preparation of well-defined reactive poly(pentafluorophenylmethacrylate) precursor particles. These particles allow orthogonalpost-modification of the internal network and the hydrophilic particle surface.As a proof-of-concept, the internal network containing reduction-cleavable crosslinkerswas functionalized with a combination of hydrophilic (acidic or basic) andhydrophobic groups to give a library of pH- and reduction-sensitive amphiphilicnanogels. Subsequently, copper-catalyzed azide-alkyne cycloaddition was used todemonstrate the attachment of azide-modified rhodamine as model compound to thesurface of the nanogels. Overall, this strategy provides a versatile platformfor the development of multi-functional amphiphilic nanogels as potentialcarriers for the delivery of hydrophobic cargoes.