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In situ formation of magnetopolymersomes via electroporation for MRI

Bain, Jennifer, Ruiz-Pérez, Lorena, Kennerley, Aneurin J., Muench, Stephen P., Thompson, Rebecca, Battaglia, Giuseppe, Staniland, Sarah S.·2015·Scientific Reports
DOI 10.1038/srep14311PMC PMC4585761
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Abstract

As the development of diagnostic/therapeutic (and combined: theranostic) nanomedicine grows, smart drug-delivery vehicles become ever more critical. Currently therapies consist of drugs tethered to, or encapsulated within nanoparticles or vesicles. There is growing interest in functionalising them with magnetic nanoparticles (MNPs) to target the therapeutics by localising them using magnetic fields. An alternating magnetic field induces remote heating of the particles (hyperthermia) triggering drug release or cell death. Furthermore, MNPs are diagnostic MRI contrast agents. There is considerable interest in MNP embedded vehicles for nanomedicine, but their development is hindered by difficulties producing consistently monodisperse MNPs and their reliable loading into vesicles. Furthermore, it is highly advantageous to "trigger" MNP production and to tune the MNP's size and magnetic response. Here we present the first example of a tuneable, switchable magnetic delivery vehicle for nanomedical application. These are comprised of robust, tailored polymer vesicles (polymersomes) embedded with superparamagnetic magnetite MNPs (magnetopolymersomes) which show good MRI contrast (R2* = 148.8 s−1) and have a vacant core for loading of therapeutics. Critically, the magnetopolymersomes are produced by a pioneering nanoreactor method whereby electroporation triggers the in situ formation of MNPs within the vesicle membrane, offering a switchable, tuneable magnetic responsive theranostic delivery vehicle.

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Figure 1 Schematic of the proposed mechanism for MNP synthesis within polymersomes using electroporation. (a), which opens pores within the membrane at which point influx of iron ions occurs in parallel with efflux of NaOH (encapsulated) (b). (c) shows the in situ room temperature co-precipitation that then occurs at the interface within the membrane.
Figure 1 Schematic of the proposed mechanism for MNP synthesis within polymersomes using electroporation. (a), which opens pores within the membrane at which point influx of iron ions occurs in parallel with efflux of NaOH (encapsulated) (b). (c) shows the in situ room temperature co-precipitation that then occurs at the interface within the membrane.CC BY · PubMed Central
Figure 2 Characterisation of the polymersomes. Comparison of two different preparation methods of the NaOH encapsulated polymersomes; Extruded and stirred. (A) DLS data sizing (B) the corresponding TEM grainsizing and (C) TEM image of an extruded polymersome sample (stained with 0.75% uranyl formate) (cryo-TEM image of stirred sample shown in Fig. 3A).
Figure 2 Characterisation of the polymersomes. Comparison of two different preparation methods of the NaOH encapsulated polymersomes; Extruded and stirred. (A) DLS data sizing (B) the corresponding TEM grainsizing and (C) TEM image of an extruded polymersome sample (stained with 0.75% uranyl formate) (cryo-TEM image of stirred sample shown in Fig. 3A).CC BY · PubMed Central
Figure 3 Analysis of magnetopolymersomes. Single particle cryo-EM images of extruded polymersomes before (A) and after (B) electroporation, with the latter displaying a high density of iron particles around the membrane. (C) shows the same sample as in (B) as imaged by room temperature TEM.
Figure 3 Analysis of magnetopolymersomes. Single particle cryo-EM images of extruded polymersomes before (A) and after (B) electroporation, with the latter displaying a high density of iron particles around the membrane. (C) shows the same sample as in (B) as imaged by room temperature TEM.CC BY · PubMed Central
Figure 4 Magnetopolymersomes show enhanced contrast in MRI imaging. 7 T magnetic resonance R2 relaxometry data (16 echoes, 9 slices, image shows 5th slice) and 7 T magnetic resonance R2* relaxometry data (12 echoes, 9 slices, image shows 5th slice). Both R2 and R2* relaxometry rates show significant differences between saline (dashes) and electroporated polymersomes (solid).
Figure 4 Magnetopolymersomes show enhanced contrast in MRI imaging. 7 T magnetic resonance R2 relaxometry data (16 echoes, 9 slices, image shows 5th slice) and 7 T magnetic resonance R2* relaxometry data (12 echoes, 9 slices, image shows 5th slice). Both R2 and R2* relaxometry rates show significant differences between saline (dashes) and electroporated polymersomes (solid).CC BY · PubMed Central

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Metadata

Authors
Bain, J., Ruiz-Pérez, L., Kennerley, A. J., Muench, S. P., Thompson, R., Battaglia, G., & Staniland, S. S.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2015-09-22
Volume
5
Issue
1
ISSN
2045-2322
DOI
10.1038/srep14311
PMC
PMC4585761
Cited by
24
References
0
Language
en
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