Theranostics of Epitaxially Condensed Colloidal Nanocrystal Clusters, through a Soft Biomineralization Route

Abstract

Clustering of biocompatible magnetic iron oxide nanocrystallites (MIONs) is a synthetic strategy which improves magnetic manipulation, imaging, and sensing for biomedical applications. In this work we describe the synthesis of condensed clustered MIONs obtained through biomineralization and epitaxial aggregation in the presence of alginate at ambient conditions, mimicking the process that so far has been achieved only by nature, in iron-oxidizing bacteria. These condensed-type magnetic nanostructures exhibit higher magnetophoretic responses compared to other types of magnetic colloids and clustered systems. The soft environmental conditions used for the synthesis of the magnetic nanosystems enables the alginate coating material to retain high drug loading ability for the doxorubicin molecule as well as strong binding proclivity for radionuclides. The strong binding of doxorubicin forms the physical basis to obtain magnetic nanocarriers, where the selective release of the drug occurs only under the action of external stimuli, such as remote magnetic hyperthermia or increased temperature (i.e., inflamed tissue). Furthermore, the strong binding proclivity of radionuclides facilitates in vivo SPECT imaging. The witnessed properties are obtained by using only ∼17 wt % alginate content in the magnetic superstructures; thus, very high saturation magnetization value is imparted to the condensed system, expressed in terms of the hybrid's mass. In spite of the fact that the magnetic nanoassemblies are characterized by low hydrodynamic diameter, ∼45 nm, the transverse relaxivity reaches the remarkable value of 250 s −1 mM −1 Fe (for negative MION contrast agents of this size), a property that validates the use of these nanostructures as effective MRI contrast agents.

Colloidal magnetic nanocrystal clusters: variable length-scale interaction mechanisms, synergetic functionalities and technological advantages

“…The balance between the opposing forces determines the size and the morphology of the secondary structures ( Figure 3). Either a perfect crystallographic orientation or a small misalignment among the incorporated particles has been found in these sorts [16,79], organometallic (C-E) [36,84,88] and biomineralization (F) [29] routes. (A) Reprinted with permission from Ref.…”

“…Different morphologies, compact or loose structures with diameters ranging from 30 to a few hundred nm have been obtained with the previous synthesis strategies. Colloidal assemblies of inorganic nanocrystals are commonly called nanoclusters [15,[21][22][23][24][25][26][27][28][29], but in the literature, they can also be found as nanoflowers [30], nanoroses [17], multi-core particles [31,32], nanoassemblies [13,14,33,34], porous particles [35], flower-like mesocrystals [36], nanobeads [37,38], and pomegranate-like particles [34]. Furthermore, it is worth noting that these can be delivered with diverse chemical origin, including nanoclusters of ZnO [39,40], Co 3 O 4 [41], CuO [42], In 2 O 3 [40], CoO [40], MnO [40], ZnSe [40], CuCr 2 S 4 [43], PbS [44], and TiO 2 [45].…”

In vitro cytotoxicity analysis of doxorubicin-loaded/superparamagnetic iron oxide colloidal nanoassemblies on MCF7 and NIH3T3 cell lines

“…15 These magnetic nanoclusters (40 nm in diameter consisting of 13 nm individual crystals of magnetite) coated with alginate display high relaxivity index in MRI (r 2 =243 mM -1 s -1 ), superparamagnetic behavior with saturation magnetization of 70 emu/g (7T, 300 K), high drug loading (26±2 wt% of DOX), high cytocompatibility, and magnetophoretic response. The binding of DOX on the surface of alginate chains is very strong (through hydrogen bonds and electrostatic interactions) allowing the release of drug only during magnetic hyperthermia or high temperature (see previous results reported in Ref.…”

“…Such a slow release might be beneficial in the in vivo scenario, since slow release might provide the necessary time to the nanocarrier to concentrate into the tumor and then release its payload (for example, through a trigger such as hyperthermia, as we have shown successfully for MagAlg in our previous publication). 15 On the other hand, systems displaying higher cytotoxicity than the free drug might result into fast in vivo …”

“…One of the main pathways that magnetic carriers are planned to act is through magnetic targeting, and MagAlg has been proven to be exceptional in magnetic manipulation with external magnetic fields as we have shown in our previous publication. 15 As a next step, we will continue with cytotoxic study of this system by using the application of external magnetic field to increase the temperature of the system, which causes the controlled drug release in the desired tumor cells and tissue.…”