Magnetic
nanostructures (MNS) have a wide range of biological applications
due to their biocompatibility, superparamagnetic properties, and customizable
composition that includes iron oxide (Fe3O4),
Zn2+, and Mn2+. However, several challenges
to the biomedical usage of MNS must still be addressed, such as formulation
stability, inability to encapsulate therapeutic payloads, and variable
clearance rates in vivo. Here, we enhance the utility of MNS during
controlled delivery applications via encapsulation within polymeric
bicontinuous nanospheres (BCNs) composed of poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS)
copolymers. PEG-b-PPS BCNs have demonstrated versatile
encapsulation and delivery capabilities for both hydrophilic and hydrophobic
payloads due to their unique and highly organized cubic phase nanoarchitecture.
MNS-embedded BCNs (MBCNs) were thus coloaded with physicochemically
diverse molecular payloads using the technique of flash nanoprecipitation
and characterized in terms of their structure and in vivo biodistribution
following intravenous administration. Retention of the internal aqueous
channels and cubic architecture of MBCNs were verified using cryogenic
transmission electron microscopy and small-angle X-ray scattering,
respectively. MBCNs demonstrated improvement in magnetic resonance
imaging (MRI) contrast enhancement (r
2 relaxivity) as compared to free MNS, which in combination with scanning
transmission electron microscopy and energy-dispersive X-ray spectroscopy
evidenced the clustering and continued access to water of MNS following
encapsulation. Furthermore, MBCNs were found to be noncytotoxic and
able to deliver their hydrophilic and hydrophobic small-molecule payloads
both in vitro and in vivo. Finally, the oxidation sensitivity of the
hydrophobic PPS block allowed MBCNs to undergo a unique, triggerable
transition in morphology into MNS-bearing micellar nanocarriers. In
summary, MBCNs are an attractive platform for the delivery of molecular
and nanoscale payloads for diverse on-demand and sustained drug delivery
applications.