saporin

Mitdank H, Tröger M, Sonntag A, Shirazi NA, Woith E, Fuchs H, Kobelt D, Walther W, Weng A (2022) Suicide nanoplasmids coding for ribosome-inactivating proteins. Eur J Pharm Sci 170:106107. doi: 10.1016/j.ejps.2021.106107

Objective: To investigate the anti-proliferative activity of suicide-nanoplasmids.

Summary: In an in vivo neuroblastoma tumor model, treated mice showed a reduced tumor growth.

Usage: Design of a suicide nanoplasmid vector with saporin.

Related Products: Saporin (Cat. #PR-01)

Ujvári B, Pytel B, Márton Z, Bognár M, Kovács LÁ, Farkas J, Gaszner T, Berta G, Kecskés A, Kormos V, Farkas B, Füredi N, Gaszner B (2022) Neurodegeneration in the centrally-projecting Edinger-Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat. J Neuroinflammation 19(1):31. doi: 10.1186/s12974-022-02399-w

Objective: To investigate whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger-Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat.

Summary: Neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson’s disease in the rat.

Usage: Leptin-SAP or unconjugated Saporin (0.08 μl) was injected into the EWcp area. This selective ablation of UCN1 neurons was used to validate the depression-like phenotype in rats. Behavioral, functional–morphological, biochemical and histopathological tools were used to test the motor coordination, mood status as well as morphological changes in the brain.

Related Products: Saporin (Cat. #PR-01), Leptin-SAP (Cat. #IT-47)

Hickerson BT, Daniels-Wells TR, Payes C, Clark LE, Candelaria PV, Bailey KW, Sefing EJ, Zink S, Ziegenbein J, Abraham J, Helguera G, Penichet ML, Gowen BB (2022) Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections. Nat Commun 13(1):558. doi: 10.1038/s41467-021-27949-3 PMID: 35091550

Objective: Demonstrate that a fusion protein of the antibody (ch128.1/IgG1) directed against the apical domain of human transferrin receptor 1 (hTfR1) and the Machupo virus (MACV) can inhibit infection of attenuated and pathogenic New World mammarenaviruses (NWMs).

Summary: NWMs cause life-threatening hemorrhagic fever (HF) and these viruses enter into cells via hTfR1. Use of ch128.1/IgG1 with other promising direct-acting small molecule antivirals or antibodies targeting the viral envelope glycoprotein would provide a complementary therapeutic strategy that would increase efficacy and reduce the emergence of drug resistance.

Usage: References MonoBiotin-ZAP reacted with avidinylated anti-hTfR (ch128.1Av) in a 1:1 molar ratio on ice for 30 minutes.

Related Products: MonoBiotin-ZAP (Cat. #BT-ZAP)

See Also:

• Daniels-Wells TR et al. Insights into the mechanism of cell death induced by saporin delivered into cancer cells by an antibody fusion protein targeting the transferrin receptor 1. Toxicol In Vitro 27(1):220-231, 2013.
• Daniels TR et al. Conjugation of an anti transferrin receptor IgG3-avidin fusion protein with biotinylated saporin results in significant enhancement of its cytotoxicity against malignant hematopoietic cells. Mol Cancer Ther 6:2995-3008, 2007.

Joshi BS, Ortiz D, Zuhorn IS (2021) Converting extracellular vesicles into nanomedicine: loading and unloading of cargo. Materials Today Nano 16:100148. doi: 10.1016/j.mtnano.2021.100148

Objective: To provide a comprehensive overview of (i) methods for the loading of EVs with therapeutic cargo, (ii) methods for EV surface functionalization to direct EVs to target cells, and (iii) methods to stimulate cargo release from EVs.

Summary: Development of methodologies to offload the natural cargo of EVs and substitute it for a cargo of interest, i.e., similar to the generation of empty viral capsids, may further aid in higher loading efficiency and enhanced therapeutic effects with improved safety.

Usage: Saporin, a small (30 kDa) ribosome-inactivating protein that induces cytotoxicity by inhibiting protein synthesis,was successfully loaded into EVs by electroporation.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Nakase I Intracellular delivery methods using biofunctional peptide-modified extracellular vesicles. Extracell Vesicles Circ Nucleic Acids 1:44, 2020. American Society for Exosomes and Microvesicles 2020 Annual Meeting

Wu B, Zhao TV, Jin K, Hu Z, Abdel MP, Warrington KJ, Goronzy JJ, Weyand CM (2021) Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation. Nat Immunol 22(12):1551-1562. doi: 10.1038/s41590-021-01065-2

Objective: To identify a deficiency of mitochondrial aspartate production as a key abnormality in autoimmune T cells.

Summary: Shortage of mitochondrial aspartate disrupted the regeneration of the metabolic cofactor nicotinamide adenine dinucleotide (NAD), causing ADP-deribosylation of the endoplasmic reticulum (ER) sensor GRP78/BiP. Transfer of intact mitochondria into T cells as well as supplementation of exogenous aspartate rescued the mitochondria-instructed expansion of ER membranes and suppressed TNF release and rheumatoid tissue inflammation.

Usage: Immunofluorescence (Permeabilization by 0.5% Saporin)

Related Products: Saporin (Cat. #PR-01)

Illath K, Kar S, Gupta P, Shinde A, Wankhar S, Tseng FG, Lim KT, Nagai M, Santra TS (2022) Microfluidic nanomaterials: From synthesis to biomedical applications. Biomaterials 280:121247. doi: 10.1016/j.biomaterials.2021.121247

Objective: To evaluate the current state of the controlled synthesis of nanomaterials using microfluidic devices.

Summary: In summary, inherent features of microfluidics enabled the controlled synthesis of biopolymer and silica nanomaterials that can easily encapsulate drugs.

Usage: Saporin was loaded quickly with nanogel of various sizes and observed that saporin loaded protein releasing depended on the density of cross-linking.

Related Products: Saporin (Cat. #PR-01)

Shramm PA, Ancheta LR, Bouajram R, Lappi DA (2021) A brief history of saporin and its contributions to neuroscience. Neuroscience 2021 Abstracts J002.11. Society for Neuroscience, Virtual.

Summary: When investigating the origins of targeted toxins (a drug, therapy, or scientific tool directed to a unique extracellular target), an appropriate place to begin is with the Nobel Prize-winning work of Paul Ehrlich and his concept of the “magic bullet.” Over 100 years later, the use of targeted toxins to perform molecular neurosurgery has become a vital practice that allows researchers to observe changes in organisms after eliminating a neuronal population. A prime example of this practice is the specific targeting of cholinergic neurons in the basal forebrain to mimic Alzheimer’s disease (AD). The research tool designed for this purpose is 192-IgG-Saporin, an antibody conjugated to the ribosome-inactivating protein (RIP) Saporin. Researchers have used this targeted toxin for over 30 years. A 2019 publication by Verkhratsky et al. reviews AD models and states this is the only lesion model that specifically targets cholinergic neurons. In 1983, during a quest to find the optimal payload for a targeted toxin, Fiorenzo Stirpe and colleagues discovered Saporin, a plant protein isolated from the common soapwort plant Saponaria officinalis. Unlike ricin and abrin, Saporin does not have a binding chain and cannot enter a cell on its own. Scientists have devised new ways to use Saporin to advance their research and drug development activities. Just a few examples include: 1. A novel suicide gene therapy approach that uses a vector encoding a double-stranded DNA aptamer to deliver the gene encoding Saporin, 2. Delivery of Saporin encapsulated in a nanotechnology system for development of cancer treatments, 3. A deeper understanding of the difference between pain and itch and the relevant pathways, and 4. Development of a stable epilepsy animal model that is used for screening specific treatments that will lead to micro-methods to eliminate the disease. This review will focus on Saporin as the payload delivered to cells. Targeted toxins (typically targeted by an antibody or peptide chemically linked or genetically fused) provide robust tools for neuroscience where ablation of specific neuronal populations is used to study behavior and function. Saporin is an ideal molecule because of its extreme resistance to high temperatures and denaturation, retention of catalytic activity after conjugation, and lack of a binding chain to allow entrance to the cytoplasm of cells on its own. As a result, it is one of the most studied RIPs used for its vigorousness, potency, safety, and ease of use in the laboratory. The information presented will shed light on the history of Saporin, current applications, and what the future holds for this protein in the neuroscience field.

Related Products: Saporin (Cat. #PR-01)

View the complete poster.

Chen X, Liu H, Li A, Ji S, Fei H (2021) Hydrophobicity-tuned anion responsiveness underlies endosomolytic cargo delivery mediated by amphipathic vehicle peptides. J Biol Chem 297(6):101364. doi: 10.1016/j.jbc.2021.101364

Objective: The study focuses on hydrophobicity and a structure-function strategy to evolve a template peptide for endosomolytic cargo delivery.

Summary: The peptide LP6 could dramatically promote cargo cell entry and facilitate cytosolic delivery of biomacromolecules such as saporin.

Usage: HeLa cells were treated with saporin (10, 20, 50μg/ml) in the absence (–) or presence (+) of LP6 (20μM) to confirm the cytosolic delivery ability of LP6.

Related Products: Saporin (Cat. #PR-01)

Lodhi MS, Khan MT, Bukhari SMH, Sabir SH, Samra ZQ, Butt H, Akram MS (2021) Probing transferrin receptor overexpression in gastric cancer mice models. ACS Omega 6(44):29893-29904. doi: 10.1021/acsomega.1c04382 PMID: 34778662

Objective: To investigate the role of the transferrin receptor, a glycoprotein receptor that is expressed many-folds on rapidly growing cells due to the greater demand of iron, in gastric cancer.

Summary: A mouse model of gastric cancer has the potential to be used in the future to study the therapeutic effects of cancer medicines, and overexpression of transferrin receptors could be identified through the designed probe to be used as diagnostics.

Related Products: MonoBiotin-ZAP (Cat. #BT-ZAP)

See Also:

• Daniels TR et al. Conjugation of an anti transferrin receptor IgG3-avidin fusion protein with biotinylated saporin results in significant enhancement of its cytotoxicity against malignant hematopoietic cells. Mol Cancer Ther 6:2995-3008, 2007.

Borkowski LF, Smith CL, Keilholz AN, Nichols NL (2021) Divergent receptor utilization is necessary for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections. J Neurophysiol 126(3):709-722. doi: 10.1152/jn.00236.2021

Objective: The authors tested the hypothesis that phrenic long-term facilitation (pLTF) following treatment with CTB-SAP is: 1) adenosine 2A (A2A) receptor-dependent at 7d; and 2) serotonin (5-HT) receptor-dependent at 28d.

Summary: This study furthers understanding of the contribution of differential receptor activation to pLTF and its implications for breathing following respiratory motor neuron death.

Usage: Male rats received bilateral, intrapleural injections of CTB-SAP or Saporin Control (25 μg).

Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)