Stable Aqueous Dispersions of Glycopeptide‐Grafted Selectably Functionalized Magnetic Nanoparticles

Abstract

Bionanomaterials have received increasing attention over the last decade, owing to their potential to advance medical science by providing novel solutions for disease diagnostics and treatment. [1] However, bionanomaterial engineering imposes considerable challenges, as significant design criteria and properties, which are dictated by the specific application, must be met. MRI-trackable magnetic nanoparticles (MNPs) and their assemblies, which are capable of targeting specific cell types, such as cancer cells, for image-guided treatment are increasingly being investigated. [2] The typical design criteria for MNPs are biomedical in nature, including cellular selectivity (biorecognition), extended blood circulation times and biocompatibility, there are also practical considerations such as processability and scalability. Additional MRI-specific criteria include colloidal stability and high image contrast. The efficacy of an MNP suspension for generating contrast by enhancing, or suppressing, a local MRI signal is quantified by the spin-lattice (r 1 ) and spin-spin (r 2 ) relaxivities, respectively. These are the water relaxation enhancement per millimolar concentration of iron. For T 1weighting applications (localized signal enhancement), r 1 must be high, and r 2 and the r 2 /r 1 ratio must be low. Particle aggregation increases the r 2 value, so T 1 -weighting can only be achieved by ensuring full MNP dispersion and long-term colloidal stability.Monosaccharides offer colloidal stability through charge and steric interactions along with the possibility of cellular targeting, and so have been used to stabilize MNPs. Recently, MNP clusters have been prepared by encapsulation of alkylstabilized MNPs using poly(maleic anhydride-alt-1-octadecene) followed by EDC coupling of aminated sugars. [3] Detailed analysis of the effect of coating on cellular uptake showed that high grafting density is critical for avoiding nonspecific cellular interaction. However, the encapsulation approach resulted in extensive aggregation, as is usually the case, thus limiting the possibility of use in a T 1 -weighting application. Aggregation was exploited in a recent report where clickable monosaccharides were used to stabilize MNP clusters using complex peptide linkers, [3] which allowed differentiation of cancer cells by quantitative profiling of carbohydrate binding through changes in T 2 (local signal suppression). In a prominent recent example, a range of phosphonate-functionalized sugars were used to fully disperse MNPs, and the effect of MNP size on the T 1 -weighting and hyperthermic properties in vitro were investigated. [4] However, only one sugar per linker was possible, thus limiting the total sugar density.Hence, there is a need for platform technologies that maximize the surface density of functional monosaccharides while allowing full MNP dispersion. Multifunctional polymers have the potential to address the first issue; there have been two recent reports of a "grafting-onto" approach for MNP modification with glycopolymers....

Tuning Sizes, Morphologies, and Magnetic Properties of Monocore Versus Multicore Iron Oxide Nanoparticles through the Controlled Addition of Water in the Polyol Synthesis

“…Large (several tens of nm) NPs were produced for MFH, while ultraultra-small superparamagnetic iron oxide (UUSPIO) NPs of few nm only were synthesized for applications as positive MRI contrast agents with T 1 -weighted sequences. [22][23][24][25] The main reaction parameter to select morphology (and therefore magnetic properties) was solvent composition. A mixture of DEG and NMDEA (1:1 volume ratio) was used to yield large NPs, while ultra-ultra-small NPs were produced in pure DEG.…”

Recent advances in biosensing using magnetic glyconanoparticles

“…Thus, control of functionalization is essential. Borase et al [42] reported a combined strategy for the glycosylation of MNPs coated with 3-aminopropyltriethoxysilane, consisting of an alkyne polymer grafting followed by click chemistry using unprotected galactosyl azide (Fig. 6).…”

“…Therefore, the nature of the carbohydrate can influence the relaxation of the water protons and the biodistribution of the nanoparticles in vivo. Although optimal T1-weighting properties have also been described for glycopeptide-stabilized superparamagnetic magnetite nanoparticles [42], most of the reports describe the use of iron oxide glycoMNPs as T2 contrast agents. The nature of the carbohydrate can also tune the transverse relaxivity (r2) values of iron oxide nanoparticles functionalized with rhamnose [24] or grafted with diblock copolymers bearing α-D-mannose, α-D-glucose or β-D-glucose [26].…”

Designing polymers with sugar-based advantages for bioactive delivery applications

“…These well-defined polymers are highly tunable and can be manipulated into different formulations (e.g., micelles, nanoparticles, vesicles, hydrogels), presenting a versatile platform for bioactive delivery. As such, sugar-based polymers have become increasingly prevalent in the broad portfolio of biomedicine and biomaterial applications [16]. …”