New method can help test vaccine formulations

Scientists from Northwestern University are casting a net for nanoparticles. They have now identified a new, rapid technique for producing nanoparticles from a simple, self-assembling polymer.

Evan Scott. Image Credit: Northwestern University.

The innovative method offers new possibilities for different kinds of applications, such as diagnostics, water purification, and rapidly generating vaccine formulations, in which many different kinds of molecules had to be either delivered or captured simultaneously.

By using a polymer net that disintegrates into nanogels, or nanoscale hydrogels, the technique can efficiently capture more than 95% of DNA, proteins, or small molecule drugs—either alone or in combinations. However, in the case of other nanoparticle delivery systems, loading efficiency is usually between 5% and 20%.

We use a polymer that forms a wide net throughout an aqueous solution. Then we induce the net to collapse. It collects anything within the solution, trapping therapeutics inside of nanogel delivery vehicles with very high efficiency.”

Evan A. Scott, Study Lead and Kay Davis Professor, Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University

Fanfan Du, a postdoctoral fellow in Scott’s laboratory, stated, “It works like a fishing net, which first spreads out due to electrostatic repulsion and then shrinks upon hydration to trap ‘fish’.”

The study was recently published in the Nature Communications journal on September 29^th, 2020.

Scott is also the Kay Davis Professor of Biomedical Engineering at the McCormick School of Engineering of Northwestern University. Monica Olvera de la Cruz and Vinayak Dravid, both professors from Northwestern University, are the study’s coauthors.

Natural molecules, like peptides and DNA, can quickly self-assemble and organize into different structures. But imitating this process using human-made polymer systems has remained largely limited. Formerly developed processes intended for self-assembling drug delivery systems are not only labor intensive and time consuming but also hard to scale. Such processes are also regrettably inefficient, causing only a small amount of the drug to actually reach inside the delivery system.

Clinical application of self-assembled nanoparticles has been limited by difficulties with scalability and with loading large or multiple therapeutics, especially proteins. We present a highly scalable mechanism that can stably load nearly any therapeutic molecule with high efficiency.”

Evan A. Scott, Study Lead and Kay Davis Professor, Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University

Scotts’ research team has now achieved success by using a polypropylene sulfone (PPSU) homopolymer, which is extremely soluble in dimethylsulfoxide (DMSO) solution, but tends to form hydrophilic and electrostatic aggregates in water. These are amphiphilic aggregates, which allow them to organize into network and ultimately disintegrate into gels.

Adding more water induces the network to collapse, leading to the formation of nanogels. The manner in which water is added affects the PPSU chain formation, which changes the nanogels’ size and structure.”

Fanfan Du, Postdoctoral Fellow, McCormick School of Engineering, Northwestern University

Atomistic simulations—which were carried out by Baofu Qiao in the Olvera de la Cruz team—established that weak sulfone-sulfone bonding stabilized the nanostructures. By applying coarse-grained simulations conducted by Trung Dac Nguyen, a postdoctoral fellow from Northwestern University, the team visualized the nanonet structures. This paves the way for soft materials assembly through sulfone-sulfone bonding.

Apart from drug delivery applications, the team also believes that the new approach could even be used for water purification. The network can collapse to gather contaminants in water, leaving the pure water behind.