Synthetic Ligand-Coated Magnetic Nanoparticles for Microfluidic Bacterial Separation from Blood

Lee, Jung-Jae; Jeong, Kwang‐Yong; Hashimoto, Michinao; Kwon, Ae‐Ran; Rwei, Alina Y.; Shankarappa, Sahadev A.; Tsui, Jonathan H.; Kohane, Daniel S.

doi:10.1021/nl3047305

Cited by 221 publications

(164 citation statements)

References 46 publications

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“…These sites could conceivably be used to attach a different biomolecule, for example, one with an orthogonal activity. Thus, our preliminary results suggest surprising versatility in this approach: quorum-sensing molecules could be simultaneously or sequentially attached in combination with other biomolecules, such as antimicrobial agents, enzymes, or perhaps quorum-sensing compounds that target other bacteria 39–41 .…”

Section: Resultsmentioning

confidence: 96%

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

et al. 2017

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Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviors including virulence factor secretion and biofilm formation. Quorum sensing relies on production, release, accumulation, and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviors. We probe this strategy using Staphylococcus aureus. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviors. We investigate key features of the compounds, linkers, and surfaces necessary to appropriately position molecules to interact with cognate receptors, and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components, and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviors of bacteria on surfaces.

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Section: Resultsmentioning

confidence: 96%

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

et al. 2017

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“…Ettp-5 fluorophore and ZnDPA with a carboxylic acid handle were synthesized as previously described (Lee et al 2014;Pansare et al 2014). PS-b-PEG was converted into PS-b-PEG modified with an amine (PS-b-PEG-NH 2 ) functional group, and conjugated with ZnDPA via carbodiimide coupling to form PS-b-PEG-ZnDPA (Supplementary methods).…”

Section: Experimental Materialsmentioning

confidence: 99%

“…Affinity and magnetic-based separation of bacteria have recently been identified as a potentially viable method to treat sepsis without the use of antimicrobials (Lee et al 2014). To assess if ZnDPA-modified NPs can be used for analogous applications, hydrophobic Fe 3 O 4 iron oxide colloids were synthesized and modified with a hydrophobic oleic acid coat such that iron oxide may be encapsulated into the core of the particles (Supplementary methods).…”

Section: Magnetically Active Npsmentioning

confidence: 99%

“…Importantly, these ligand targets are not found on the surface of healthy mammalian cells, which allows for specific binding and imaging of bacteria with minimal background signals when using these targeting ligands in vivo (Rice et al 2015;van Oosten et al 2013). Recent novel uses of targeted NPs include the binding and magnetic separation of bacteria from solution to treat bacterial sepsis, by passing NPs through custom-made microfluidic devices (Lee et al 2014). However, the use of microfuidics for the filtering of blood may be infeasible due to he large blood volumes and flow rates required for processing, relative to the volumes and flow rates ammenable to microfluidic processing.…”

Section: Introductionmentioning

confidence: 99%

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Nanoparticle targeting of Gram-positive and Gram-negative bacteria for magnetic-based separations of bacterial pathogens

Yang

Wilson

et al. 2017

Appl Nanosci

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Antimicrobial resistance is a healthcare problem of increasing significance, and there is increasing interest in developing new tools to address bacterial infections. Bacteria-targeting nanoparticles hold promise to improve drug efficacy, compliance, and safety. In addition, nanoparticles can also be used for novel applications, such as bacterial imaging or bioseperations. We here present the use of a scalable block-copolymer-directed self-assembly process, Flash NanoPrecipitation, to form zinc(II)-bis(dipicolylamine) modified nanoparticles that bind to both Grampositive and Gram-negative bacteria with specificity. Particles have tunable surface ligand densities that change particle avidity and binding efficacy. A variety of materials can be encapsulated into the core of the particles, such as optical dyes or iron oxide colloids, to produce imageable and magnetically active bacterial targeting constructs. As a proof-of-concept, these particles are used to bind and separate bacteria from solution in a magnetic column. Magnetic manipulation and separation would translate to a platform for pathogen identification or removal. These magnetic and targeted nanoparticles enable new methods to address bacterial infections.

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“…The binding of Zn-DPAmodified magnetic nanoparticles to S. aureus to form aggregates has already been reported. 30 However, this study is the first to clarify the effect of metal species on the aggregate formation with S. aureus. A similar effect of metal species on the aggregate formation with Escherichia coli was noted (See SI).…”

mentioning

confidence: 92%

Staphylococcus aureusDetection by Fluorescent Silica Nanoparticles Modified with Metal–Dipicolylamine Complexes

et al. 2016

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We have developed a new method for Staphylococcus aureus (S. aureus) detection, which employs fluorescent silica nanoparticles (FSiNPs) modified with metaldipicolylamine complex (M-dpa-HCC). Among the M-dpa-HCC/FSiNP complexes, Cu-dpa-HCC/FSiNP formed large aggregates with S. aureus in 10 min, which were easily observed by the naked eye. The antibacterial activity of Cu-dpa-HCC/FSiNP was also confirmed. 46 However, the culture method requires nearly five days for detection, whereas the other two methods are expensive and require expertise in handling.710 Therefore, the development of a new method for simple and rapid detection of bacteria has been actively pursued. To this end, various biosensors have been developed. 11 In particular, nanoparticle sensors are promising because their surfaces and chemical structures are easily controlled and various types of recognition sites can be introduced on the nanoparticle surface. 12,13 In addition, the nanoparticles are inexpensive, have low toxicity, and can be easily handed. 14,15 It is well known that many phosphate groups exist on the phosphatides on bacterial cell surfaces. 16 It has been reported that dipicolylamine fluorophores show diverse fluorescence responses by changing the metal species. 1719 We have developed fluorescent silica nanoparticles (FSiNPs) possessing metaldipicolylamine binding sites with coumarin fluorophore (M-dpa-HCC ( Figure 1A)), for selective phosphate recognition in water. By altering the metal species in the M-dpa-HCC/ FSiNP complexes ( Figure 1B) 25 The importance of not only simple detection of pathogenic bacteria but also high antibacterial activity for preventing infections has become widely acknowledged. 2628Herein we report an efficient method for S. aureus detection, which employs M-dpa-HCC/FSiNP complexes. Depending on the metal species in the DPA complexes, the M-dpa-HCC/ FSiNP complexes exhibited specific affinity for the anionic surface of bacteria, forming large fluorescent aggregates that were easily observed by the naked eye. The antibacterial activity of the Cu-dpa-HCC/FSiNP complex for S. aureus was also confirmed.The design of bacteria-sensitive nanoparticles was initiated with the synthesis of FSiNPs according to the Stöber method, 29 using tetraethyl orthosilicate (TEOS) and tris(2,2¤-bipyridyl)ruthenium(II) complexes (fluorescence core) as the precursor. The surface of FSiNPs was modified with 3-aminopropyltrimethoxysilane (APS) and was reacted with dpa-HCC by DMT-MM to obtain dpa-HCC/FSiNP (See Supporting Information (SI)). To evaluate the effect of dpa-HCC-coordinated metal species on bacterial recognition, the aggregation behavior of S. aureus upon the addition of M-dpa-HCC/FSiNP (M = Cu 2+ or Zn 2+ ) complexes was examined. Figure 2 shows the confocal fluorescence images of S. aureus treated with (1) metal-free dpa-HCC/FSiNP (Figures 2A2D), (2) Cu-dpa-HCC/FSiNP (Figures 2E2H), and (3) Zn-dpa-HCC/FSiNP (Figures 2I 2L). The samples were prepared by mixing S. aureus (10 8 CFU mL ¹1 ) with M-dpa-HCC/FSiNP (1 mg mL ...

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Synthetic Ligand-Coated Magnetic Nanoparticles for Microfluidic Bacterial Separation from Blood

Cited by 221 publications

References 46 publications

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

Nanoparticle targeting of Gram-positive and Gram-negative bacteria for magnetic-based separations of bacterial pathogens

Staphylococcus aureusDetection by Fluorescent Silica Nanoparticles Modified with Metal–Dipicolylamine Complexes

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