Magnetic Nanostructure-Loaded Bicontinuous Nanospheres Support Multicargo Intracellular Delivery and Oxidation-Responsive Morphological Transitions

Abstract

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.

The Combination of Morphology and Surface Chemistry Defines the Immunological Identity of Nanocarriers in Human Blood

“…We first assessed protein adsorption to the nine nanocarrier types and investigated whether their physicochemical properties alter the composition of the protein coronas formed in human plasma ( Figure A). Our past studies demonstrate that PEG‐ b ‐PPS nanocarriers exhibit good serum and in vivo stability, [ 17,28,33,34,66,67 ] and polymersomes of MeO, OH, and Phos surface chemistry are stable in complex with serum albumin, serum protein mixtures, and in blood protein exchange experiments. [ 17 ] Here, we first developed and validated an ultracentrifugation‐based procedure for isolating all PEG‐ b ‐PPS nanocarrier chassis types following corona formation (Figure 2A).…”

Vaccination with mycobacterial lipid loaded nanoparticle leads to lipid antigen persistence and memory differentiation of antigen-specific T cells

“…Furthermore, we found that after MA-BCN vaccination, MA could persist for 6 weeks post-vaccination within alveolar macrophages, a phenomenon which was dependent on the presence of an encapsulating vector, nanocarrier or bacterial, but not the route of vaccination. Due to the enhanced stability of the BCN architecture that can support the loading of diverse and multiple payloads [22, 32], we were able to efficiently co-encapsulate within BCN both MA and Ag85B, an immunodominant protein antigen of Mtb [33]. Interestingly, while both antigens activated their corresponding antigen-specific T cells, only MA resulted in antigen persistence, suggesting a potentially unique characteristic of subunit vaccines containing lipid antigens.…”

Scaling Up Magnetic Nanobead Synthesis with Improved Stability for Biomedical Applications

“…This effect arises from the cumulative magnetic moments of all individual particles while the nanoobject remains mostly superparamagnetic. Several groups have proposed various nanobead preparation and functionalization methods to make multitasking materials exploitable in preclinical studies for diagnosis and treatment of diseases. , Also in our group we have developed a robust method for the synthesis of nanobeads with control over core and surface properties, and we have tested them as nanoplatforms in several in vitro applications. − To mention some examples of applications, by decorating our magnetic nanobeads with a thermoresponsive polymer, we were able to load and release chemo-therapeutic drugs entrapped in the polymer . Here the release was based on a change in the temperature of the solution from 37 °C to 47 °C .…”