Abstract
Nanoparticulate agents for magnetic drug delivery systems (DDSs) have extensive applications in targeted drug delivery, contrast imaging and therapeutics. However, no simple synthetic method for magnetic DDS agents has been developed without the need to add magnetic nanoparticles. Here, we describe the one-step fabrication of ‘all-in-one’ magneto-assemblies using an ‘inorganic-metal-salt-free’ method, involving spontaneous self-assembly of the water-insoluble prodrug μ-oxo-bis(N,N′-ethylenebis(salicylideniminato)iron) [Fe(salen)] (magnetic core) with polypyrrole (PPy)-b-polycaprolactone (PCL) smart diblock copolymers. In the system, PCL serves as a heat-responsive core scaffold, and PPy serves as an electronic core-size controller and pH-responsive shell. This core–shell nanocomposite has a high-loading capacity (~90%), and the core size is tunable by incorporating albumin or gum arabic as bio-coating agents, which also provide colloidal stability, biocompatibility and thermo-stability. Fe(salen), which has intrinsic antitumor activity, also has ubiquitous magnetic properties, which are dramatically enhanced in these molecular assemblies with magnetic coupling. Moreover, these multifunctional nanoassemblies can be delivered magnetically, can serve as magnetic resonance imaging contrast agents, can generate magneto-hyperthermal effects and can enable magnetic field-triggered release of Fe(salen) molecules under acidic conditions.
Highlights
We have recently explored the in vivo magnetic guided hyperthermia method,[14] showing effective alternating magnetic field (AMF)-heating by injecting a concentration of only ~ 30 μM, which makes us believe that the given bovine serum albumin (BSA)-CSNA samples could enable improved hyperthermic performance in future pre-clinical stages
In summary, instead of using iron-oxide NPs as an exclusive mainstay for conventional magnetic drug delivery systems (DDSs) platforms, we have developed a simple and convenient method for preparing micelle-like CSNA composites loaded with Fe(salen), which has both intrinsic antitumor activity and magnetic properties
These single-drug CSNAs have a large loading capacity and exhibit stable colloidal properties because they contain lightweight drug molecules rather than inorganic metal NPs. They are readily core-and surface-modifiable with BSA or gum arabic (GA), giving them extraordinary physico-chemical versatility: they are highly soluble in water, easy to process, biocompatible and magnetically tunable
Summary
The synthesis of MNPs with desirable magnetic properties for magnetic DDS platforms requires numerous steps to control the particles’ core, diameter, anisotropy, suspension composition and surface coating,[1,2,3,4,5,6,7,8,9] and requires considerable care to avoid adverse effects in vivo. Metal complexes are useful for this purpose[13,14,15,16] because a metal complex is small and can be therapeutically active with magnetic[13,14] or optical properties.[15,16] a single-step fabrication method for a metal-salt-free, magnetic metal-complex-based local DDS platform might shift the synthetic paradigm to realize advanced DDS applications
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