TY - JOUR
T1 - Magnetic Nanostructure-Loaded Bicontinuous Nanospheres Support Multicargo Intracellular Delivery and Oxidation-Responsive Morphological Transitions
AU - Modak, Mallika
AU - Bobbala, Sharan
AU - Lescott, Chamille
AU - Liu, Yu Gang
AU - Nandwana, Vikas
AU - Dravid, Vinayak P.
AU - Scott, Evan A.
N1 - Funding Information:
This research was supported by the National Science Foundation grant 1453576, the National Institutes of Health Director’s New Innovator Award no. 1DP2HL132390-01, and the American Heart Association Award 19IPLOl34760491. This work made use of the BioCryo and Keck-II facilities of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); and the State of Illinois, through the IIN. It also made use of the CryoCluster equipment, which has received support from the MRI program (NSF DMR-1229693). This work was supported by the Northwestern University—Flow Cytometry Core Facility supported by Cancer Center Support Grant (NCI CA060553). Metal analysis was performed at the Northwestern University Quantitative Bio-element Imaging Center generously supported by NASA Ames Research Center NNA06CB93G. Animal imaging work was performed at the Northwestern University Center for Advanced Molecular Imaging generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. Cellular microscopy was performed at the Biological Imaging Facility at Northwestern University (RRID:SCR_017767), graciously supported by the Chemistry for Life Processes Institute, the NU Office for Research, and the Department of Molecular Biosciences. SAXS experiments were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, E.I. DuPont de Nemours & Co., and The Dow Chemical Company. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract no. DE-AC02-06CH11357.
Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/12/16
Y1 - 2020/12/16
N2 - 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 (r2 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.
AB - 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 (r2 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.
KW - bicontinuous nanospheres
KW - drug delivery
KW - magnetic nanostructures
KW - nanoparticle
KW - oxidation responsive
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U2 - 10.1021/acsami.0c15920
DO - 10.1021/acsami.0c15920
M3 - Article
C2 - 33259182
AN - SCOPUS:85097761547
SN - 1944-8244
VL - 12
SP - 55584
EP - 55595
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
IS - 50
ER -