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.
Highlights
The amphiphilic block copolymer was synthesized by the polymerization of ethylene oxide (PEO) and butadiene (PBD) monomers
PBD (1300)-PEO (2500) was chosen for polymersome synthesis as previous studies had shown the production of monodisperse unilamellar vesicles, within the required size range for this system[24,25,26]
It should be noted that there is a discrepancy between the Dynamic light scattering (DLS) and Transmission electron microscopy (TEM) sizing, but importantly the population distribution is in agreement
Summary
The magnetism can be exploited for therapeutic magnetic hyperthermia treatments, in which MNPs exposed to a time varying magnetic field gives rise to magnetically induced heating, and the subsequent destruction of surrounding tissue and/ or release of heat activated drugs, which have the potential for both conjugation to the polymersome exterior or to be encapsulated within the vesicle core[10,16,17] All these elements can be combined to give a multipurpose “theranostic” nanomedicine. The magnetopolymersomes developed to date rely on a multistep process of crystallising and processing MNPs, subsequent loading into polymer vesicles[9,19] For this crystallisation step, iron-oxide MNPs can be produced by various methods leading to differing size, shape and population heterogeneity[18]. This opens up extensive engineering opportunities with respect to MNP/polymersome properties for various applications
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