A Chemical structure of PPSU showing the polymer backbone and oxygen atoms that
carry positive/negative (blue/red) atomic partial charges, respectively. b
Atomistic simulation snapshot showing a dissolution-complementarity equilibrium
in DMSO for six PPSU20 chains. Inset is a superstructure formed by PPSU self-
complementarity. c PPSU self-complementarity leading to a 2D reversible
superstructure with enrichment of oxygen atoms on the surface. Formation of 3D
superstructures is inhibited in DMSO due to the strong repulsion among layers.
d Average dipolar energies per dipole-dipole pair of sulfone–sulfone and
sulfone-solvent. Error bars represent the standard deviation from three
parallel simulations. e Atomistic simulation snapshot showing the formation of
a 3D superstructure through PPSU bundling in water. Inset showing the 3D
superstructure with or without water molecules. Credit: Nature Communications
(2020). DOI: 10.1038/s41467-020-18657-5.
The team
has discovered a new, rapid method for fabricating nanoparticles from a simple,
self-assembling polymer. The novel method presents new possibilities for
diverse applications, including water purification, diagnostics and rapidly
generating vaccine formulations, which typically require many different types
of molecules to be either captured or delivered at the same time.
Using a
polymer net that collapses into nanoscale hydrogels (or nanogels), the method
efficiently captures over 95% of proteins, DNA or small molecule drugs—alone or
in combinations. By comparison, loading efficiency is typically between 5% and
20% for other nanoparticle delivery systems.
"We
use a polymer that forms a wide net throughout an aqueous solution," said
Northwestern's Evan A. Scott, who led the study. "Then we induce the net
to collapse. It collects anything within the solution, trapping therapeutics
inside of nanogel delivery vehicles with very high efficiency."
"It
works like a fishing net, which first spreads out due to electrostatic
repulsion and then shrinks upon hydration to trap 'fish,'" added Fanfan
Du, a postdoctoral fellow in Scott's laboratory.
The paper
was published last week (Sept. 29) in the journal Nature Communications.
Scott is
the Kay Davis Professor of Biomedical Engineering at Northwestern's McCormick
School of Engineering. Northwestern professors Monica Olvera de la Cruz and
Vinayak Dravid coauthored the paper.
Molecules
found in nature, such as DNA and peptides, can rapidly self-assemble and
organize into diverse structures. Mimicking this process using human-made polymer
systems, however, has remained limited. Previously developed processes for
self-assembling drug delivery systems are time consuming, labor intensive and
difficult to scale. The processes also tend to be woefully inefficient,
culminating in a small fraction of the drug actually making it 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," Scott said. "We present a highly scalable mechanism that
can stably load nearly any therapeutic molecule with high efficiency."
Scott's
team found success by using a polypropylene sulfone (PPSU) homopolymer, which
is highly soluble in dimethylsulfoxide (DMSO) solution, but forms electrostatic
and hydrophilic aggregates in water. The aggregates are amphiphilic, which
causes them to assemble into networks and eventually collapse into gels.
"Adding
more water induces the network to collapse, leading to the formation of nanogels,"
Du said. "The manner in which water is added affects the PPSU chain
formation, which changes the nanogels' size and structure."
Atomistic
simulations—performed by Baofu Qiao in the Olvera de la Cruz group—confirmed
that the nanostructures were stabilized by weak sulfone-sulfone bonding. Using
coarse-grained simulations performed by Northwestern postdoctoral fellow Trung
Dac Nguyen, the researchers observed the nanonet structures. This opens a new
avenue for soft materials assembly by means of sulfone-sulfone bonding.
In
addition to drug delivery applications, the researchers also believe the novel
method could be used for water purification. The network could collapse to
collect contaminants in water, leaving pure water behind.