Short communicationSynthesis of pseudopolyrotaxanes-coated Superparamagnetic Iron Oxide Nanoparticles as new MRI contrast agent
Graphical abstract
Highlights
► Synthesis of novel hybrid nanostructured systems possibly useful for medical imaging and drug delivery. ► The SPIONs@PRs hybrid nanomaterials present a transverse relaxivity higher than the commercial compound, Endorem®. ► The prepared particles have multi-task biological capabilities.
Introduction
Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have been recognized as a powerful tool for various biomedical applications such as targeted drug delivery [1], [2], contrast agents for Magnetic Resonance Imaging (MRI) [3], [4], [5], [6], [7], [8], and as effector agents capable of eliciting hyperthermia [9], cell/protein separation [10], and tissue repair [11]. To facilitate the contrast of the MRI images, which is crucial issue for precise detection, contrast agents (CAs) are employed [8], [12], [13], [14], [15], [16], [17]. Although the gadolinium chelates are recognized as the most common compounds used as CAs, their usage are limited due to the toxicity issues and low targeting capability [3]. Due to their low-toxicity, targeting capability, and multi-tasking potential (e.g. simultaneous capabilities such as drug delivery, hyperthermia, and gene therapy), multifunctional SPIONs are extensively going to be recognized as promising candidate for medical imaging [1], [18].
One of the drawbacks of SPIONs as drug carriers is their rapid removal from the body by the reticulo-endothelial system, which ultimately impairs the targeting and delivery of drugs using such an approach. Therefore, in order to increase the performance and safety of the SPIONs for biomedical applications, new coatings have been developed [11], [19]. In addition to increasing biocompatibility, non-immunogenicity and stability in biological systems, the following specific goals are targets of the newly developed coating systems: (i) multiple therapeutic compound conjugation on the surface of nanoparticles (NPs); (ii) enhancement of the effective interaction with target cells; (iii) site-specific release of diagnostic and/or therapeutic agents, and (iv) controlled release drug delivery [20]. For instance, the crosslinked poly(ethylene glycol)-co-fumarate coating was employed on the surface of SPIONs, in order to reduce the fast drug release from the surface of nanoparticles [19]. The results confirmed a 21% reduction of the burst release of Tamoxifen citrate, an estrogen receptor antagonist, loaded on the crosslinked coating of SPIONs compared with non-crosslinked NPs [19]. Amiri et al. [21] reported similar results on the reduction of burst effect of various drugs (e.g. Tamoxifen and Doxorubicin) by application of crosslinked poly(ethylene glycol)-co-fumarate coating on the surface of colloidal nanocrystal clusters of SPIONs.
Polyrotaxanes (PRs) are highly functional supramolecules consisting of several rings bound to one or more axes, in which the dissociation of rings from the axis is often hindered by bulky groups, the so-called stoppers, at both ends of the axis [22], [23], [24], [25], [26], [27], [28], [29], [30]. It is notable that PRs without stoppers are called pseudopolyrotaxanes (PPRs). These rings can slide or rotate around the axis which gives them an incredible capability to be used in multivalent drug delivery where multiple ligands conjugated to the drug carrier interact with multiple receptors. They also offer a large number of hydroxyl groups available for conjugation with drugs.
Due to these unique properties, PRs and PPRs have attracted enormous interest as carriers in drug delivery [31], [32] and gene delivery [33] fields. Recently, it has been found that non-covalent interactions between PRs and metal NPs or quantum dots lead to core–shell architectures, due to the conversion of the conformation of PRs from extended to circular shape [34].
In this study, PPRs consisting of polyethylene glycol (PEG) axis and α-cyclodextrin rings were used as new shells for SPIONs in order to create new biocompatible SPIONs@PRs hybrid nanomaterials with enhanced functionality. α-Cyclodextrin rings are FDA approved and PEG is an inert polymer, therefore PPRs consisting of them are biocompatible coating. Carbohydrate backbone of the PRs shell has the following advantages: (i) improving the stability of the SPIONs in the biological medium, (ii) increasing the SPIONs’ interactions and consequently faster transfer through the cell membrane, (iii) increasing the SPIONs functionality and biocompatibility to deliver different therapeutic agents.
In conclusion, due to their biocompatible and highly functional shell, the synthesized SPIONs@PRs hybrid nanomaterials are proposed as an excellent candidate for a wide variety of biomedical applications such as imaging and targeted drug delivery.
Section snippets
Materials
Polyethylene glycol (MW = 1000), cyanuric chloride (1,3,5-trichloro-2,4,6-triazine), sodium hydroxide, iron salts, dichloromethane, diethyl ether and α-cyclodextrin were purchased from Merck. The morphology of the particles was investigated by Transmission Electron Microscopy (TEM) (ZEISS, EM-10C, Germany) operating at 100 kV. To prepare samples, a drop of suspension was placed on a copper grid and air-dried. Fourier Transform Infrared (FTIR) spectra were recorded on KBr pellets using an ABB Bomem
Results and discussion
Due to the long lengths, strand-type topology, small diameters, high functionality, biocompatibility, and their ability to wrap around NPs, pseudopolyrotaxanes were used to modify the physicochemical and biological properties necessary for obtaining a higher efficacy in the biomedical applications of magnetic NPs.
Harada and Kamachi [39] tested different molecular weights of PEG for synthesis of pseudopolyrotaxanes with α-cyclodextrins and they found out the optimal molecular weight to be 1000.
Conclusion
In this article, we detail the synthesis of novel hybrid nanostructured systems as promising candidates for multi-task biomedical applications, such as medical imaging and drug delivery. Non-covalent interactions, mainly hydrogen bonding, between pseudopolyrotaxanes consisting of polyethylene glycol axis and α-cyclodextrin rings; and hydroxyl functional groups at the surface of iron oxide NPs led to new core@shell hybrid nanomaterials. These hybrid magnetic NPs can be further functionalized for
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