Magnetic metal-complex-conducting copolymer core–shell nanoassemblies for a single-drug anticancer platform

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. A one-step chemical reaction can produce high-capacity nanocomposites for drug delivery with intrinsic antitumor and magnetic activity. Magnetic nanoparticles impart imaging and on-demand release capabilities to drug-delivery polymers, but can be tricky to incorporate into biocompatible materials without adversely affecting solubility. Jeong-Hwan Kim from Yokohama City University Graduate School of Medicine in Japan and co-workers overcame this synthetic challenge by switching from typical iron oxide nanomagnets to ones based on ‘iron-salen’ molecular magnets with demonstrated cancer-fighting ability. The team discovered a procedure that self-assembles them into nanospheres encapsulated by an outer layer of polypyrrole polymers. These core-shell hybrid nanospheres could be readily modified by albumin or gum arabic biocoating agents to improve their solubility, stability, and magnetism, when loaded with drugs. Multifunctional magnetic capabilities, including MR imaging, magnetic field- and pH-responsive heat-releasing hyperthermia effects, and controlled release, were also found. Magneto-core–shell nanoassemblies by loading μ-oxo-bridged Fe complex (Fe(salen) (core)) inside PCL-b-PPy block copolymers (shell) are fabricated, without the use of common magnetites and toxic solvents. By taking a surface functionalization with natural biomolecules (bovine serum albumin/gum arabic (BSA/GA)), the nanoassemblies endow to hold tunablity of core-size and magnetism, biocompatibility, and colloidal stability. Moreover, distinguishing their multifunctional features of cancer targeting include magneto-guided drug delivery, MRI, and triggered hyperthermia in responsive to multi (magnetic, thermo, and pH) stimuli, which allow them a promising potential for a wide-variety of ‘minimally-invasive’ theranostic clinics, as an alternative candidate to conventional magnetite-based anticancer targeting.