Magnetic Glyco-nanoparticles:  A Unique Tool for Rapid Pathogen Detection, Decontamination, and Strain Differentiation

Abstract

The appealing mechanisms by which nanocomposites knit biomolecules not only lend credence in designing novel nanosensors but considerably advance medical applications. 1 Recent headline news about Escherichia coli (E. coli) contamination in produce and Bacillus anthracis attacks pinpoint the urgent need for an effective method for microbial decontamination and rapid detection without time-consuming cell culturing. It is known that many bacteria use mammalian cell surface carbohydrates as anchors for attachments, which subsequently results in infection. 2 The unique combination of magnetic nanocomposites and diverse carbohydrate bioactivities prompts us to embark on a biosensing research program. Herein, we report a magnetic glyco-nanoparticle (MGNP)-based system to not only detect E. coli within 5 min, but also remove up to 88% of the target bacteria from the medium. Furthermore, the identities of three different E. coli strains were easily determined on the basis of the response patterns to two MGNPs highlighting their potential in biosensing.It is advantageous to use magnetic nanoparticles (NPs) for detection. The high surface/volume ratio offers more contact surface area for attaching carbohydrates and for capturing pathogens. 3 The sizes of NPs are typically about 2 orders of magnitude smaller than a bacterium, which allows the attachment of multiple NPs onto a bacterial cell rendering easy magnet-mediated separation. 3,4 Moreover, the small NPs have faster kinetics in solution as compared to their micrometer-sized counterparts, which can result in fast detection.Our journey commenced with functionalization of silica-coated magnetite NP (NP 1) with D-mannose (Man) through either a triazole linker (MGNP 2) formed by the [2+3] Huisgen reaction 5 or an amide linkage (MGNP 3) (Schemes 1 and S1). With our covalent approach, 6 all carbohydrates are uniformly oriented on the NP surface, which is crucial for high performances in cell-capturing studies. 7 All MGNPs were characterized by X-ray diffraction, transmission electron microscopy (TEM), thermogravimetric analyses, and IR spectroscopy ( Figures S1-4).To ensure that carbohydrates on MGNP retain their binding abilities, the interaction between various MGNPs with a mannose binding lectin, concanavalin A (Con A), 8 was first investigated. Carbohydrate-lectin interaction 9 is central in devising our biosensor. After mixing NPs with fluorescein-labeled Con A, a magnetic field was applied to the mixture through a handheld magnet inducing aggregation of magnetic NPs on the side of the vial. The residual fluorescence of supernatants was then recorded ( Figure S5). With MGNP 3, the emission intensity of the supernatant decreased 87% indicating that most Con A was removed by 3. Triazole linked MGNP 2 was less efficient accounting for a 60% emission decrease probably because of the low efficiency of the Huisgen reaction with immobilized alkynes. 5 NP 1 without carbohydrates (control) did not remove any Con A, proving that the separation of Con A is due to its interaction...

The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications

“…However, during this cross-linking process, the irreversible formation of aggregates can be observed, limiting the use of the resultant IONPs. Th e functionalization of IONPs using silane chemistry is versatile, involving the use of many functional silanes available commercially, such as alcohol, amine and thiol, which are useful for further biofunctionalization using small biocompounds [12] and carbohydrates [13].…”

Water-Dispersible Sugar-Coated Iron Oxide Nanoparticles. An Evaluation of their Relaxometric and Magnetic Hyperthermia Properties

“…26 Moreover, membrane-bound receptors, such as lectins, are known to assist material internalization inside the cell via endocytosis following the binding of their ligand. 27 Some examples of saccharide-coated iron oxide NPs have been reported: these include the attachment on Fe 3 O 4 NPs of dihydroxyborylphenyl groups functionalized with different mono-and oligosaccharides, 28 the grafting of silica-coated Fe 3 O 4 NPs with functionalized D-mannose through a triazol linker, 29 the noncovalent coating of iron oxide NPs with poly(D,L-lactide-co-glycoside) via emulsion techniques, 30 or the co-precipitation of iron salts in the presence of D-mannose. 31 We have recently reported a new approach to achieve size controlled water-dispersible magnetic iron oxide NPs covalently linked to monosaccharide molecules via a phosphonate moiety.…”

Galactose-functionalized Magnetic Iron-oxide Nanoparticles for Enrichment and Detection of Ricin Toxin

“…The synthesis protocol of the galactose linker was performed in four steps according to literatures, 13,22,23 with some modifications. O-Acetyl protected galactose was subsequently bromopropyl substituted, azido substituted, hydrogenation, acylation and deacetylation (Scheme 1).…”

“…11,12 The development of saccharide-functionalized material is thus attracting much more attention in the protein-related research field. For example, sugar-functionalized magnetite (Fe3O4) has been used for rapid detection, decontamination, and strain differentiation of pathogen, 13 which is exactly benefited from lectin-saccharide interaction between the glycoproteins and glycolipids receptors expressed on the cell surfaces of pathogens and mono-or disaccharides-functionalized capturing modules. Another case is glyco-modified quantum dots, which have been synthesized and applied as a specific fluorescent label for probing glycoprotein cell receptors.…”