saporin

154 entries

Self-assembly of epitope-tagged proteins and antibodies for delivering biologics to antigen presenting cells

Gong S, Qiu J, Thayumanavan S (2023) Self-assembly of epitope-tagged proteins and antibodies for delivering biologics to antigen presenting cells. J Am Chem Soc doi: 10.1021/jacs.3c09334 PMID: 38147631

Objective: To describe a simple self-assembly strategy for generating artificial immune complexes.

Summary: The built-in recognition domains in the antibody, viz. the Fab and Fc domains, are judiciously leveraged for cargo conjugation to generate the nanoassembly and macrophage targeting, respectively. A responsive linker is engineered into the nanoassembly for releasing the protein cargo inside the macrophages while ensuring stability during delivery.

Usage: Cytotoxicity assay to measure cell death with targeted saporin.

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

Intracellular protein delivery: Approaches, challenges, and clinical applications

Chan A, Tsourkas A (2024) Intracellular protein delivery: Approaches, challenges, and clinical applications. BME Frontiers doi: 10.34133/bmef.0035

Objective: To review progress made towards achieving cytosolic delivery of recombinant proteins and possible strategies to enable proteins to cross cell membranes.

Summary: Drug delivery researchers have worked to deliver saporin into tumor cells in the hopes of producing potent next-generation cancer therapeutics. Cationic, anionic, and zwitterionic versions of poly(β-amino ester) have been developed for delivery of saporin. Chemically-modified saporin can be encapsulated by cationic LNPs for in vivo tumor inhibition. Saporin has been used as a model cargo protein for in vivo delivery via fluoropolymer nanoparticles for successful tumor growth inhibition.

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

See Also:

Exploring the potential of nanogels: From drug carriers to radiopharmaceutical agents

Kubeil M, Suzuki Y, Casulli MA, Kamal R, Hashimoto T, Bachmann M, Hayashita T, Stephan H (2023) Exploring the potential of nanogels: From drug carriers to radiopharmaceutical agents. Adv Healthc Mater e2301404. doi: 10.1002/adhm.202301404 PMID: 37717209

Summary: This review provides a brief overview of current developments of nanogels in the fields of drug delivery, therapeutic applications, tissue engineering and sensor systems. The authors described one development using saporin. Mimicking the function of molecular chaperones, Kawasaki et al. created magnetic in vivo protein transport nanogels with encapsulated iron oxide nanoparticles. The nanogels also contained saporin, which was rapidly released by an exchange reaction with serum protein. The evaluation using an oral cancer model revealed a reduction in tumor volume and suppression of tumor regrowth, with no change in body weight.

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

See Also:

  • Kawasaki R et al. (2021) Magnetically navigated protein transduction in vivo using iron oxide-nanogel chaperone hybrid. Adv Healthc Mater 10(9):e2001988. doi: 10.1002/adhm.202001988 PMID: 33694289

Emerging non-viral vectors for gene delivery

Wang C, Pan C, Yong H, Wang F, Bo T, Zhao Y, Ma B, He W, Li M (2023) Emerging non-viral vectors for gene delivery. J Nanobiotechnology 21(1):272. doi: 10.1186/s12951-023-02044-5 PMID: 37592351

Summary: This review describes the fastest-growing and efficient non-viral gene delivery vectors that include liposomes and lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). One group designed and synthesized HPAEs with positive and negative charges to deliver saporin. Another group performed cell experiments that demonstrated that a boronic acid-grafted dendrimer vector had good delivery ability for saporin.

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

The gut-brain axis mediates bacterial driven modulation of reward signaling

Kim JS, Williams KC, Kirkland RA, Schade R, Freeman KG, Cawthon CR, Rautmann AW, Smith JM, Edwards GL, Glenn TC, Holmes PV, de Lartigue G, de La Serre CB (2023) The gut-brain axis mediates bacterial driven modulation of reward signaling. Mol Metab 26:101764. doi: 10.1016/j.molmet.2023.101764 PMID: 37380023

Objective: To investigate the role of gut microbiota and vagal signaling in modulating brain dopamine reward pathways and appetitive feeding behavior.

Summary: The study found that high-fat diet and transfer of high-fat microbiota to germ-free rats reduced dopamine signaling and motivated feeding behavior compared to chow-fed and low-fat microbiota groups. Vagal deafferentation restored dopamine signaling and feeding motivation in high-fat microbiota rats, indicating gut bacteria signals that dampen reward are vagally mediated.

Usage: Animals were injected bilaterally into the nodose ganglion with either Saporin or CCK-SAP. A pulled glass micropipette containing either CCK-SAP (240 ng/ml in 0.1 M phosphate buffer) or SAP alone was inserted under the sheath of the cervical vagus and into the NG, the injection was done with a pressure-injector into two sites (one proximal and one distal, total volume, 1 µl).

Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)

Intracellular delivery of therapeutic proteins. New advancements and future directions

Porello I, Cellesi F (2023) Intracellular delivery of therapeutic proteins. New advancements and future directions. Front Bioeng Biotechnol 11:1211798. doi: 10.3389/fbioe.2023.1211798 PMID: 37304137

Objective: To provide a brief overview of the current methods for intracellular protein delivery to mammalian cells.

Summary: The field of intracellular protein delivery is still a relatively young area of research and further advancements in this field will require the integration of chemistry, materials science, formulation science, nanomedicine, and biomedical engineering.

Usage: Saporin was referenced as a molecule with the advantage of being able to block the synthesis of proteins in cells.

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

Which type of RIP is saporin?

Q: I read on your website that, “There are two types of RIPs: type I, which are much less cytotoxic due to the lack of the B chain and type II, which are distinguished from type I RIPs by the presence of the B chain and their ability to enter cells on their own.”

In the IT-27 Streptavidin-ZAP product, which type of saporin is there? Is it both type I and type II because the saporin is purified from the plant, or is it one specific type only in the product.

A: All saporin molecules are Type I ribosome-inactivating proteins. We only use saporin. An example of a Type II RIP is ricin, which can enter a cell on its own and has been used throughout history as a method of assassination.

Streptavidin-ZAP is streptavidin attached to saporin. On its own it has no way to get inside a cell. By mixing Streptavidin-ZAP with a biotinylated molecule that is recognized on the cell surface, the resulting conjugate is able to bind and internalize saporin into a cell. Once inside saporin inactivates the ribosomes which causes cell death.

From immunotoxins to suicide toxin delivery approaches: Is there a clinical opportunity? 

Ardini M, Vago R, Fabbrini MS, Ippoliti R (2022) From immunotoxins to suicide toxin delivery approaches: Is there a clinical opportunity?. Toxins (Basel) 14(9):579. doi: 10.3390/toxins14090579 PMID: 36136517

Objective: To give an overview describing some of the bacterial and plant enzymes studied so far for their delivery and controlled expression in tumor models.

Summary: “Suicide gene” therapy (SGT), consists of the selective delivery of genes coding for toxic proteins, into target cancer cells. This new and promising approach may overcome some of the issues related to the use of chemical agents (chemotherapy) such as as specificity, high dosages with accompanying side effects, and chemoresistance induction.

RIPpore: A novel host-derived method for the identification of ricin intoxication through oxford nanopore direct RNA sequencing

Ryan Y, Harrison A, Trivett H, Hartley C, David J, Clark GC, Hiscox JA (2022) RIPpore: A novel host-derived method for the identification of ricin intoxication through oxford nanopore direct RNA sequencing. Toxins (Basel) 14(7):470. doi: 10.3390/toxins14070470

Objective: The Depurination event could be detected using Oxford Nanopore Technologies (ONT) direct RNA sequencing, detecting a change in charge in the ricin loop.

Summary: Collectively, this work highlights the potential for ONT and direct RNA sequencing to detect and quantify depurination events caused by ribosome-inactivating proteins such as ricin.

Usage: Saporin was added as described by Rust et al., at 100 nM [22] for 24 h.

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

See Also:

Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs.

Li Y, Ye Z, Yang H, Xu Q (2022) Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs. Acta Pharm Sin B 12(6):2624-2639. doi: 10.1016/j.apsb.2022.04.013

Objective: To highlight the recent progress in combinatorial lipid nanoparticles (LNPs) with novel structures and properties for the delivery of small- and macromolecular therapeutics.

Summary: The administration of protein/LNP negatively impacted reproduction in rats, including sperm production, estrous cyclicity and testicular and ovarian morphology, without causing any significant side effects. This non-surgical approach can be developed into a safe and convenient strategy for controlling the overproduction of pet and wildlife.

Usage: Intravenous administration of saporin loaded LNPs

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

Maintenance mechanism of nociplastic pain in males

McDonough KE (2022) Maintenance mechanism of nociplastic pain in males. University of Texas Medical Branch Thesis.

Objective: The objective of this dissertation is to elucidate the sex-specific mechanisms underlying the transition to and maintenance of a nociplastic pain state using animal models.

Summary: This PhD dissertation investigates the mechanisms underlying the transition from acute to chronic nociplastic pain using murine models. The study finds that in males, spinal microglial activation driven by GABAergic disinhibition allows normally innocuous stimulation to induce a transition to nociplastic pain maintained by spinal microglia and proinflammatory cytokines.

Usage: Intrathecal injection of Saporin or Mac-1-SAP at 8.85 μM.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Saporin as a commercial reagent: its uses and unexpected impacts in the biological sciences-tools from the plant kingdom

Ancheta LR, Shramm PA, Bouajram R, Higgins D, Lappi DA (2022) Saporin as a commercial reagent: its uses and unexpected impacts in the biological sciences-tools from the plant kingdom. Toxins (Basel) 14(3):184. doi: 10.3390/toxins14030184

Read complete article.

Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats.

Xu L, Füredi N, Lutter C, Geenen B, Pétervári E, Balaskó M, Dénes Á, Kovács KJ, Gaszner B, Kozicz T (2022) Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats. Neuropharmacology 205:108898. doi: 10.1016/j.neuropharm.2021.108898

Objective: To show that leptin bound to neurons of the Edinger-Westphal nucleus (EWcp) stimulated STAT3 phosphorylation and increases urocortin 1 (Ucn1)-production in a time-dependent manner.

Summary: EWcp/LepRb/Ucn1 neurons respond to leptin signaling as well as control white adipose tissue size and fat metabolism without altering food intake.

Usage: Ablation of EWcp leptin receptor (LepRb) positive neurons with leptin-saporin. Either unconjugated saporin (53 ng in 80 nl MQ, or Leptin-SAP (90 ng in 80 nl MQ, was injected into the rat midbrain.

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

Suicide nanoplasmids coding for ribosome-inactivating proteins

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)

Neurodegeneration in the centrally-projecting Edinger-Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat

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)

Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections

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

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:

Converting extracellular vesicles into nanomedicine: loading and unloading of cargo

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:

Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation.

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)

Microfluidic nanomaterials: From synthesis to biomedical applications.

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)

A brief history of saporin and its contributions to neuroscience

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.

Shopping Cart
Scroll to Top