In the last decade the progress achieved on the synthesis of inorganic nanostructures has been accompanied by the parallel exploitation of these systems in various fields, among them are biology and ...medicine. We provide here an overview of the iron-based inorganic nanostructured materials that have been developed and tested in these fields. We will highlight the major concepts on the preparation, physical properties and applications of such nanostructures, starting from the most investigated iron oxide nanoparticles. We will describe then the new generation of inorganic hybrid nanostructures, which are structures that integrate in each nano-object multiple inorganic nanocrystals of different materials. In our discussion we will focus on those works that have provided a sound proof of concept on the potential of the various systems as diagnostic and therapeutic agents.
The growing interest in multifunctional nano-objects based on polymers and magnetic nanoparticles for biomedical applications motivated us to develop a scale-up protocol to increase the yield of ...polymeric magnetic nanobeads while aiming at keeping the structural features at optimal conditions. The protocol was applied to two different types of magnetic ferrite nanoparticles: the Mn-ferrite selected for their properties as contrast agents in magnetic resonance imaging and iron oxide nanostar shaped nanoparticles chosen for their heat performance in magnetic hyperthermia. At the same time, some experiments on surface functionalization of nanobeads with amino modified polyethyelene glycol (PEG) molecules have provided further insight into the formation mechanism of magnetic nanobeads and the need to cross-link the polymer shell to improve the stability of the beads, making them more suitable for further manipulation and use. The present work summarizes the most important parameters required to be controlled for the upscaling of nanobead synthesis in a bench protocol and proposes an alternative cross-linking strategy based on prefunctionalization of the polymer prior to the nanobead formation as a key parameter to improve the nanobead structural stability in solutions at different pHs and during surface functionalization.
Abstract Magnetic hyperthermia mediated by magnetic nanomaterials is one promising antitumoral nanotherapy, particularly for its ability to remotely destroy deep tumors. More and more new ...nanomaterials are being developed for this purpose, with improved heat-generating properties in solution. However, although the ultimate target of these treatments is the tumor cell, the heating efficiency, and the underlying mechanisms, are rarely studied in the cellular environment. Here we attempt to fill this gap by making systematic measurements of both hyperthermia and magnetism in controlled cell environments, using a wide range of nanomaterials. In particular, we report a systematic fall in the heating efficiency for nanomaterials associated with tumour cells. Real-time measurements showed that this loss of heat-generating power occurred very rapidly, within a matter of minutes. The fall in heating correlated with the magnetic characterization of the samples, demonstrating a complete inhibition of the Brownian relaxation in cellular conditions.
Magnetic hyperthermia (MHT) and photothermal therapy (PTT) are emergent state‐of‐the‐art modalities for thermal treatment of cancer. While their mechanisms of action have distinct physical bases, ...both approaches rely on nanoparticle‐mediated remote onset of thermotherapy. Yet, are the two heating techniques interchangeable? Here, the heating obtained either with MHT or with PTT is compared. The heating is assessed in distinct environments and involves a set of nanomaterials differing in shape (spheres, cubes, stars, shells, and rods) as well as in composition (maghemite, magnetite, cobalt ferrite, and gold). The nanoparticle's heating efficacy in an aqueous medium is first evaluated. Subsequently, the heating efficiency within the cellular environment, where intracellular processing markedly decreases MHT, is compared. Conversely, endosomal sequestration could have a positive effect on PTT. Finally, iron oxide nanocubes and gold nanostars are compared in MHT and PTT in vivo within the heterogeneous intratumoral environment. Overall, two distinct therapeutic approaches, related to high dosage allowing MHT and low dosage associated with PTT, are identified. It is also demonstrated that PTT mediated by magnetic nanoparticles has an efficacy that is comparable to that of plasmonic nanoparticles, but only at significant nanoparticle dosages. At low concentrations, only plasmonic nanoparticles can deliver a therapeutic heating.
Heat generation is compared for a panel of magnetic and plasmonic nanoparticles, under both magnetic hyperthermia (MHT) and photothermal (PTT) procedures, and in environments of increasing biological complexity. The findings prove that MHT and PTT do not work in the same windows of applicability, and that magnetic nanoparticles are “noble” adversaries to state‐of‐the‐art gold nanoparticles intended for PTT.
Ubiquitous in nature, polyamines (PAs) are a class of low-molecular aliphatic amines critically involved in cell growth, survival and differentiation. The polycation behavior is validated as a ...successful strategy in delivery systems to enhance oligonucleotide loading and cellular uptake. In this study, the chemical features and the functional roles of the PA spermidine are synergistically exploited in the synthesis and bioactive functionalization of SiO
-based structures. Inspired by biosilicification, the role of spermidine is assessed both as catalyst and template in a biomimetic one-pot synthesis of dense silica-based particles (SPs) and as a competitive agent in an interfacial reassembly strategy, to empty out SPs and generate spermidine-decorated hollow silica nanoporous pods (spd-SNPs). Spermidine bioactivity is then employed for targeting tumor cell over-expressed polyamine transport system (PTS) and for effective delivery of functional miRNA into melanoma cells. Spermidine decoration promotes spd-SNP cell internalization mediated by PTS and along with hollow structure enhances oligonucleotide loading. Accordingly, the functional delivery of the tumor suppressor miR-34a 3p resulted in intracellular accumulation of histone-complexed DNA fragments associated with apoptosis. Overall, the results highlight the potential of spd-SNP as a multi-agent anticancer therapy.
Bioencapsulation involves the envelopment of bioactive compounds or cells to host and protect them from chemical/physical degradation and biological attack from hazardous species or undesired immune ...responses ...
Magnetic liposomes offer opportunities as theranostic systems. The prerequisite for efficient imaging, tissue targeting or hyperthermia is high magnetic load of these vesicles. Here we describe the ...preparation of Ultra Magnetic Liposomes (UMLs), which may encapsulate iron oxide nanoparticles in a volume fraction of up to 30%. This remarkable magnetic charge provides UMLs with high magnetic mobilities, MRI relaxivities, and heating capacities for magnetic hyperthermia. Moreover, these UMLs are rapidly and efficiently internalized by cultured tumor cells and, when they are administered to mice, they can be vectorized to tumors by an external magnet.
Besides the study and the medical application of iron oxide nanoparticles, ferrites produced with zinc and manganese are of particular interest for their properties. The introduction of these ...elements into the crystalline structure of the magnetic particle generates some changes in the material properties, enhancing their potential use in theranostic applications. This review will cover the most important aspects of the preparation of these materials, taking into account the different methods of synthesis, and will analyze the most promising results in their use in MRI, magnetic hyperthermia and other emerging applications.
Inorganic nanoparticles have great potential for application in many fields, including nanomedicine. Within this class of materials, inorganic nanoheterostructures (NHS) look particularly promising ...as they can be formulated as the combination of different domains; this can lead to nanosystems with different functional properties, which, therefore, can perform different functions at the same time. This review reports on the latest development in the synthesis of advanced NHS for biomedicine and on the tests of their functional properties in in vivo studies. The literature discussed here focuses on the diagnostic and therapeutic applications with special emphasis on cancer. Considering the diagnostics, a description of the NHS for cancer imaging and multimodal imaging is reported; more specifically, NHS for magnetic resonance, computed tomography and luminescence imaging are considered. As for the therapeutics, NHS employed in magnetic hyperthermia or photothermal therapies are reported. Examples of NHS for cancer theranostics are also presented, emphasizing their dual usability in vivo, as imaging and therapeutic tools. Overall, NHS show a great potential for biomedicine application; further studies, however, are necessary regarding the safety associated to their use.
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