References

Goodman RL, Moore AM, Onslow K, Hileman SM, Hardy SL, Bowdridge EC, Walters BA, Agus S, Griesgraber MJ, Aerts EG, Lehman MN, Coolen LM (2023) Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep. Endocrinology 164(11):bqad148. doi: 10.1210/endocr/bqad148 PMID: 37776515

Objective: To test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells.

Summary: Injection of NK3-SAP (NKB-SAP) ablated over 90% of the KNDy cells, Kiss-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval. The findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.

Usage: Saporin conjugates were injected into the arcuate nucleus. Kiss-SAP (kisspeptin54-SAP) was diluted to 700 ng/μL in PBS immediately before use. In preliminary work to test the effectiveness of Kiss-SAP, a single unilateral injection (1 μL of 700 ng/μL) of this conjugate was made in the preoptic area of 3 ewes. The contralateral side was used as control and either received no injections or Blank-SAP (1 μL of 700 ng/μL) (IT-21).

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2024) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther 30(3):e14446. doi: 10.1111/cns.14446 PMID: 37721421

Objective: To investigate the effect of norepinephrine on the activation of brain cells through adrenergic α2 receptor, to regulate the nociception threshold in a 6-OHDA-induced animal model of Parkinson’s disease (PD).

Summary: The change of norepinephrine content can affect the activation of prefrontal and cingulate gyrus glial cells and participate in the regulation of nociception threshold in PD rats. Adrenergic α2 receptor agonist and central presynaptic membrane α2 receptor blocker both affect cell activation and improve hyperalgesia.

Usage: 4 μL of Anti-DBH-saporin was injected into the right lateral ventricle (1.25 μg/μL, 0.9% NaCl dilution), and injected at the rate of 1 μL/min.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

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

Thongchot S, Aksonnam K, Thuwajit P, Yenchitsomanus PT, Thuwajit C (2023) Nucleolin‑based targeting strategies in cancer treatment: Focus on cancer immunotherapy (Review). Int J Mol Med 52(3):81. doi: 10.3892/ijmm.2023.5284 PMID: 37477132

Objective: The authors review the mechanisms through which the multiple functions of NCL can participate in the progression of cancer. In addition, the studies that define the utility of NCL‑dependent anticancer therapies are summarized, with specific focus being paid to cancer immunotherapeutic approaches.

Summary: NCL is a multifunctional protein abundantly distributed in the nucleus, cytoplasm and cell membrane. It influences carcinogenesis, and the proliferation, survival and metastasis of cancer cells, leading to cancer progression. The overexpression of nucleolin (NCL) in a number of types of cancer provides an attractive antigen target for the development of novel anticancer immunotherapeutic treatments.

Usage: The mice were treated with 0.5 mg/kg body weight of SAP-N6L via intraperitoneal injection.

See Also:

• Dhez AC et al. Targeted therapy of human glioblastoma via delivery of a toxin through a peptide directed to cell surface nucleolin. J Cell Physiol 233(5):4091-4105, 2018.

Marquez J (2023) PTGFRN as a target for antibody-drug conjugate (ADC) development in mesothelioma and medulloblastoma. Univ Maryland Baltimore Thesis.

Objective: To investigate the role of Prostaglandin F2 Receptor Negative (PTGFRN) regulator in cancer progression and develop an antibody-drug conjugate (ADC) targeting PTGFRN for the treatment of mesothelioma and pediatric medulloblastoma.

Summary: This dissertation explores the expression and function of PTGFRN in mesothelioma and pediatric medulloblastoma, identifying its association with aggressive cancer phenotypes. The study further develops a potent ADC using a PTGFRN-specific monoclonal antibody conjugated to the cytotoxic compound Duocarmycin, demonstrating significant anti-cancer efficacy in both in vitro and in vivo models .

Usage: Both a custom direct conjugate and Fab-ZAP Mouse (IT-48) were used (up to 10 nM) on transfected HEK-293A cells.

Related Products: Fab-ZAP mouse (Cat. #IT-48), Custom Conjugates

Metz M, Kolkhir P, Altrichter S, Siebenhaar F, Levi-Schaffer F, Youngblood BA, Church MK, Maurer M (2023) Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases. Allergy doi: 10.1111/all.15850 PMID: 37605867

Objective: Authors review the role of mast cells (MC) in the pathogenesis of chronic urticaria (CU), explore current therapeutic strategies, and introduce the concept of MC silencing as a strategy to block activation of MCs without eliciting immunosuppressive adverse effects.

Summary: CU is a MC-dependent disease with limited therapeutic options. Current strategies are directed at inhibiting IgE-mediated activation of MCs. MC depletion or silencing strategies are being developed to overcome limitations of singularly targeted agents. MC silencers, such as monoclonal antibodies that engage inhibitory receptor like sialic acid-binding immunoglobulin-like lectin8 (Siglec-8) have reached preclinical stages of development. Siglecs have been shown to be internalized upon antibody engagement, such as Siglec-8, and is being used to deplete MCs via conjugating saporin to the internalizing Siglec-8 antibody to cause cell death in human mast cells.

Usage: Usage: Anti-Siglec-8 (2C4)-SAP was used at 2.5 µg/ml to eliminate eosinophils and at 1.25 µg/ml to eliminate the HMC-1.2 human mast cell line.

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

See Also:

• O’Sullivan J et al. Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells. J Allergy Clin Immunol 141:1774-1785.e1777, 2018.

Dobryakova YV, Gerasimov K, Spivak YS, Korotkova T, Koryagina A, Deryabina A, Markevich VA, Bolshakov AP (2023) The induction of long-term potentiation by medial septum activation under urethane anesthesia can alter gene expression in the hippocampus. Int J Mol Sci 24(16):12970. doi: 10.3390/ijms241612970 PMID: 37629149

Related Products: 192-IgG-SAP (Cat. #IT-01)

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)

Miles AJ, Drew ED, Wallace BA (2023) DichroIDP: a method for analyses of intrinsically disordered proteins using circular dichroism spectroscopy. Commun Biol 6(1):823. doi: 10.1038/s42003-023-05178-2 PMID: 37553525

Objective: To use DichroIDP software to analyze secondary structures of proteins containing disordered structures via circular dichroism spectroscopy.

Summary: Globular proteins have specific shapes and mainly contain standard secondary structures. In contrast, intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) have flexible chains with limited persistent secondary structures.

Usage: Saporin is used to study secondary and tertiary protein structure

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

Jorgensen MD (2023) Designing coiled-coil peptide materials for biomedical applications. Purdue University Thesis.

Objective: Using saporin [PR-01] containing hydrogel to target and eliminate cancer cells.

Summary: Hydrogels can bind molecular cargo and be used to shuttle cytotoxic drugs across the body. Using a pH-responsive hyaluronic acid nanogel containing saporin, cancer cells with overexpressed CD44 receptor are eliminated.

Related Products: Saporin (Cat. #PR-01), Anti-CD44-SAP (Cat. #IT-72)

See Also:

• Ding L, Jiang Y, Zhang J, Klok HA, Zhong Z (2018) pH-Sensitive Coiled-Coil Peptide-Cross-Linked Hyaluronic Acid Nanogels: Synthesis and Targeted Intracellular Protein Delivery to CD44 Positive Cancer Cells. Biomacromolecules 19(2):555-562. doi: 10.1021/acs.biomac.7b01664 PMID: 29284258