In the realm of soft nanotechnology, hydrogel micro‐ and nanoparticles represent a versatile class of responsive materials. Over the last decade, our group has investigated the synthesis and physicochemical properties of a variety of synthetic hydrogel particles. From these efforts, several particle types have emerged with potentially enabling features for biological applications, including nanogels for targeted drug delivery, microlenses for biosensing, and coatings for biomedical devices. For example, core/shell nanogels have been used to encapsulate and deliver small interfering RNA to ovarian cancer cells; nanogels used in this fashion may improve therapeutic outcomes for a variety of macromolecular therapeutics. Microgels arranged as multilayers on implantable biomaterials greatly minimize the host inflammatory response to the material. Furthermore, the triggered release of drugs (i.e., insulin) has been demonstrated from similar assemblies. The goal of this feature article is to highlight developments in the design of responsive microgels and nanogels in the context of our recent efforts and in relation to the community that has grown up around this fascinating class of materials.
Deformation of 570-nm radius poly(N-isopropylacrylamide-co-acrylic acid) microgels passing through individual 375- to 915-nm radius nanopores in glass has been investigated by the resistive-pulse method. Particle translocation through nanopores of dimensions smaller than the microgel yields electrical signatures reflecting the dynamics of microgel deformation. Translocation rates, and event duration and peak shape, are functions of the conductivities of microgel and electrolyte. Our results demonstrate that nanopore resistive-pulse methods provide new fundamental insights into microgel permeation through porous membranes.
We describe the straightforward synthesis of "clickable" multiresponsive microgels containing both carboxylic acid groups and azidohydrin or terminal alkyne groups, via a one-pot multistage polymerization approach. The clickable functional groups on the microgels were confirmed by FTIR. Additionally, we simultaneously performed "click" and acid-amine coupling reactions on microgels with fluorescent dyes containing complementary functional groups. Epifluorescence microscopy was employed to confirm the coupling of those dyes to the microgels. The orthogonality of the click reaction to other functional groups such as hydroxyl, carboxylic acid, and amino groups was confirmed, suggesting the potential utility of such microgels in applications where multifunctional colloidal particles are required.
To enhance the immunogenicity of the Influenza H5N1 vaccine, we developed an oil-in-water nanoemulsion (NE) adjuvant. NE displayed good temperature stability and maintained particle size. More importantly, it significantly enhanced IL-6 and MCP-1 production to recruit innate cells, including neutrophils, monocytes/macrophages and dendritic cells to the local environment. Furthermore, NE enhanced dendritic cell function to induce robust antigen-specific T and B cell immune responses. NE-adjuvanted H5N1 vaccine not only elicited significantly higher and long-lasting antibody responses, but also conferred enhanced protection against homologous clade 1 as well as heterologous clade 2 H5N1 virus challenge in young as well as in aged mice. The pre-existing immunity to seasonal influenza did not affect the immunogenicity of NE-adjuvanted H5N1 vaccine.
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