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

Liu, He Zhu; Tang, Ji Jun; Xiao, Xi; Guo, Lei; Xie, Jian; Wang, Yu Xia

doi:10.2116/analsci.27.19

Cited by 22 publications

(11 citation statements)

References 28 publications

(21 reference statements)

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“…The use of microarrays, which include panels of antibodies for simultaneous detection of a variety of antigenic targets of interest, allowed multiplexed detection of ricin in parallel with other harmful toxic agents, such as cholera toxin, staphylococcal enterotoxins A and B, Bacillus globigii, botulinum toxin A, Yersinia pestis, and heat labile toxin of Escherichia coli, and provided dramatic improvements in assay utility and flexibility (Delehanty and Ligler, 2002;Garber et al, 2010;Simonova et al, 2012;Wadkins et al, 1998;Weingart et al, 2012). In other works, the toxin capture antibodies used as receptors were substituted by DNA/RNA aptamers (Haes et al, 2006;Kirby et al, 2004;Lamont et al, 2011), single domain antibodies (Anderson et al, 2013;Shia and Bailey, 2013;Stine et al, 2005), and sugar-conjugated materials (Huebner et al, 2013;Liu et al, 2011). By bypassing traditional antibodies, improvements can be made in regard to reagent stability and storage life.…”

Section: Methods That Cannot Identify Biologically Active Ricinmentioning

confidence: 99%

“…Notably, by complementing ricin-specific sample enrichment steps with RTA enzyme activity assays, ricin could be selectively identified while confirming A-chain activity in parallel (Becher et al, 2007;Bevilacqua et al, 2010;He et al, 2010;May et al, 1989), allowing distinction from nontoxic monomeric type 1 RIP toxins. In addition to anti-ricin antibodies, ricin-specific RNA aptamers (Haes et al, 2006;Kirby et al, 2004;Lamont et al, 2011) and carbohydrate compounds (Huebner et al, 2013;Liu et al, 2011) have also been evaluated for recovering ricin from suspect contaminated samples (Blome and Schengrund, 2008;Stine et al, 2005;Uzawa et al, 2008). Carbohydrate ligands selectively bind to the ricin B-chain.…”

Section: Methods That Can Identify Biologically Active Ricinmentioning

confidence: 99%

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Ricin detection: Tracking active toxin

Bozza

Tolleson

Rosado

et al. 2015

Biotechnology Advances

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Ricin is a plant toxin with high bioterrorism potential due to its natural abundance and potency in inducing cell death. Early detection of the active toxin is essential for developing appropriate countermeasures. Here we review concepts for designing ricin detection methods, including mechanism of action of the toxin, advantages and disadvantages of current detection assays, and perspectives on the future development of rapid and reliable methods for detecting ricin in environmental samples.

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Section: Methods That Cannot Identify Biologically Active Ricinmentioning

confidence: 99%

Section: Methods That Can Identify Biologically Active Ricinmentioning

confidence: 99%

Ricin detection: Tracking active toxin

Bozza

Tolleson

Rosado

et al. 2015

Biotechnology Advances

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“…Lactose-modified Sepharose has been used for purification of abrin . Recently, paramagnetic nanoparticles modified with galactose and lactose-modified monolithic silica were both used for the affinity enrichment of ricin. , …”

mentioning

confidence: 99%

Identification of RIP-II Toxins by Affinity Enrichment, Enzymatic Digestion and LC-MS

et al. 2014

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Type 2 ribosome-inactivating protein toxins (RIP-II toxins) were enriched and purified prior to enzymatic digestion and LC-MS analysis. The enrichment of the RIP-II family of plant proteins, such as ricin, abrin, viscumin, and volkensin was based on their affinity for galactosyl moieties. A macroporous chromatographic material was modified with a galactose-terminated substituent and packed into miniaturized columns that were used in a chromatographic system to achieve up to 1000-fold toxin enrichment. The galactose affinity of the RIP-II proteins enabled their selective enrichment from water, beverages, and extracts of powder and wipe samples. The enriched fractions were digested with trypsin and RIP-II peptides were identified based on accurate mass LC-MS data. Their identities were unambiguously confirmed by LC-MS/MS product ion scans of peptides unique to each of the toxins. The LC-MS detection limit achieved for ricin target peptides was 10 amol and the corresponding detection limit for the full method was 10 fmol/mL (0.6 ng/mL). The affinity enrichment method was applied to samples from a forensic investigation into a case involving the illegal production of ricin and abrin toxins.T ype 2 ribosome-inactivating proteins (RIP-II toxins) are a class of plant toxins that includes a number of potent chem-bio threat agents, such as ricin (Ricinus communis), abrin (Abrus precatorius), viscumin (Viscum album), modeccin (Adenia digitata), and volkensin (Adenia volkensii). RIP-II toxins are heterodimeric proteins that consist of an enzymatically active N-glycosidase A chain connected to a B chain via a disulfide bond. The B chain is a lectin with carbohydrate binding domains that have an affinity for galactose-terminated surface receptors on eukaryotic cells. Binding promotes the uptake of the toxin into the cell by endocytosis, where a part intriguingly finds its way via the Golgi complex to the endoplasmatic reticulum. From there the A subunit is translocated into the cytosol, where it hydrolyses the Nglycosidic bond between an adenine residue and ribose at a specific position in 28S rRNA and thereby inhibits protein synthesis, eventually causing cell death.

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“…One of them is also common to RCA 120 (T6). The identity of these peptides was published previously . A B‐chain tryptic peptide is not required as a marker to intact ricin protein due to the affinity of ricin's B‐chain to the LA beads which clearly indicates its presence.…”

Section: Resultsmentioning

confidence: 99%

“…Purification of ricin using modified Sepharose with galactose was originally described by Simmons and Russell . Paramagnetic nanoparticles modified with galactose were also used for ricin enrichment . Recently, affinity enrichment methods using lactose‐modified monolithic silica or galactose‐modified chromatographic material were combined with accurate mass LC‐MS/MS analysis for the identification of ricin tryptic peptides.…”

Section: Introductionmentioning

confidence: 99%

Rapid and sensitive identification of ricin in environmental samples based on lactamyl agarose beads using LC‐MS/MS (MRM)

et al. 2019

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Ricin, a plant-derived toxin extracted from the seeds of Ricinus communis (castor bean plant), is one of the most toxic proteins known. Ricin's high toxicity, widespread availability, and ease of its extraction make it a potential agent for bioterrorist attacks.Most ricin detection methods are based on immunoassays. These methods may suffer from low efficiency in matrices containing interfering substances, or from false positive results due to antibody cross reactivity, with highly homologous proteins. In this study, we have developed a simple, rapid, sensitive, and selective mass spectrometry assay, for the identification of ricin in complex environmental samples. This assay involves three main stages: (a) Ricin affinity capture by commercial lactamyl-agarose (LA) beads. (b) Tryptic digestion. (c) LC-MS/MS (MRM) analysis of tryptic fragments. The assay was validated using 60 diverse environmental samples such as soil, asphalt, and vegetation, taken from various geographic regions. The assay's selectivity was established in the presence of high concentrations of competing lectin interferences.Based on our findings, we have defined strict criteria for unambiguous identification of ricin. Our novel method, which combines affinity capture beads followed by MRM-based analysis, enabled the identification of 1 ppb ricin spiked into complex environmental matrices. This methodology has the potential to be extended for the identification of ricin in body fluids from individuals exposed (deliberately or accidentally) to the toxin, contaminated food or for the detection of the entire family of RIP-II toxins, by applying multiplex format.

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

Cited by 22 publications

References 28 publications

Ricin detection: Tracking active toxin

Ricin detection: Tracking active toxin

Identification of RIP-II Toxins by Affinity Enrichment, Enzymatic Digestion and LC-MS

Rapid and sensitive identification of ricin in environmental samples based on lactamyl agarose beads using LC‐MS/MS (MRM)

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