Engineering the Size of Bicontinuous Nanospheres via Multi-Inlet Vortex Mixing

Bicontinuous nanospheres
(BCNs) are self-assembled nanostructures
with interconnected aqueous channels that enable the coloading of
hydrophilic and hydrophobic cargo; however, their size has been difficult
to control. Here, we present a scalable approach to tune the size
distribution of poly(ethylene glycol)-b-poly(propylene
sulfide) BCNs using a multi-inlet vortex mixer. Higher mixing times
and polymer concentrations produced larger BCNs, while shorter mixing
times and lower concentrations yielded spherical micelles. Small-angle
X-ray scattering and cryogenic transmission electron microscopy confirmed
the BCN bicontinuous morphology, which persisted at smaller sizes.
The porous BCN structure resulted in increased surface roughness compared
to polymersomes (PSs). In vitro, BCNs and PSs of
comparable sizes recruited distinct protein coronas early, but their
profiles showed convergence by 24 h. In vivo, organ
biodistribution was determined primarily by the nanocarrier size rather
than the morphology. These findings establish a robust approach to
BCN fabrication while revealing dynamic biological interactions that
inform nanocarrier design.