References

Allred CA, Gormley C, Venugopal I, Li S, McGuire MJ, Brown KC (2023) Tumor-specific intracellular delivery: peptide-guided transport of a catalytic toxin. Commun Biol 6(1):60. doi: 10.1038/s42003-022-04385-7 PMID: 36650239

Objective: The demonstration of a peptide optimized by chemical modifications for tumor specificity to deliver saporin, a catalytic toxin, specifically to cancer cells via both in vitro and in vivo.

Summary: Peptides rival antibodies in affinity and specificity and offer an alternative as cancer-targeting molecules. In comparison to antibodies, peptides have a faster development time and lower production cost. The authors isolated peptide MGS4, derived from a phage-displayed library using a non-small cell lung cancer (NSCLC) cell line as the target. MGS4 was modified to identify the minimal binding domain while also improving affinity and stability. Importantly, the authors provide data showing the peptide delivered saporin both in vitro and in vivo to cancer cells demonstrating anti-tumor efficacy in a mouse model.

Usage: In vitro delivery was performed by reacting biotinylated peptide with Streptavidin-ZAP (Cat. #IT-27) in a 1:1 molar ratio. Cells were treated for 6h at 37C. The drug was removed and replaced with media and after 72 hours, cell viability was measured with CellTiter-GLO. In vivo delivery was performed using biotinylated MGS4 reacted with Streptavidin-ZAP and administered via tail-veil injection (7.5 ug/100 ul) 2x/week for 2.5 weeks for a total of 5 treatments.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Ivanova D, O’Byrne KT (2024) New methods to investigate the GnRH pulse generator. J Mol Endocrinol 72(2):e230079. doi: 10.1530/JME-23-0079 PMID: 38085702

Objective: To review the latest methodologies and insights into the GnRH pulse generator and its role in regulating reproductive hormone secretion.

Summary: The paper discusses recent advancements in understanding the GnRH pulse generator and its role in reproductive hormone secretion. It highlights the involvement of kisspeptin/neurokinin B/dynorphin (KNDy) neurons and the use of advanced techniques like genetic mouse models, electrophysiology, optogenetics, and calcium imaging. These findings enhance our comprehension of the KNDy network’s oscillatory behavior and its regulation by gonadal steroids, which is crucial for developing better infertility treatments.

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

See Also:

• Helena C et al. KNDy neurons modulate the magnitude of the steroid-induced luteinizing hormone surges in ovariectomized rats. Endocrinology 156:4200-4213, 2015.

Maiarù M, Leese C, Silva-Hucha S, Fontana-Giusti S, Tait L, Tamagnini F, Davletov B, Hunt SP (2024) Substance P-botulinum mediates long-term silencing of pain pathways that can be re-instated with a second injection of the construct in mice. J Pain 25(6):104466. doi: 10.1016/j.jpain.2024.01.331 PMID: 38218509

Summary: The authors discuss how Substance P-Botulinum is used to try to replicate the permanent results achieved with Substance P-Saporin (SP-SAP, SSP-SAP).

Related Products: SSP-SAP (Cat. #IT-11)

See Also:

• Mantyh PW et al. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279, 1997.
• Nichols ML et al. Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science 286:1558-1561, 1999.
• Brown DC et al. Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185, 2013.
• Wiley RG et al. Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar(9),Met(O(2))(11)]-substance P-saporin: Behavioral and anatomical analyses. Neuroscience 146:1333-1345, 2007.
• Vierck CJ et al. Comparison of operant escape and innate reflex responses to nociceptive skin temperatures produced by heat and cold stimulation of rats. Behav Neurosci. 2004;118(3):627-35.

McDougle M, de Araujo A, Singh A, Yang M, Braga I, Paille V, Mendez-Hernandez R, Vergara M, Woodie LN, Gour A, Sharma A, Urs N, Warren B, de Lartigue G (2024) Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metab 36:1-15. doi: 10.1016/j.cmet.2023.12.014 PMID: 38242133

Objective: To investigate the separate gut-brain circuits for sugar and fat reinforcement and their combined effect on overeating.

Summary: This study reveals that intestinal fats and sugars are sensed by distinct vagal populations, each engaging separate central reward circuits to cause dopamine release and reinforcement. Combining fat and sugar triggers both circuits, leading to increased dopamine efflux and promoting overeating, highlighting a subconscious drive to consume obesogenic diets.

Usage: 0.5 µl of CCK-SAP (IT-31) or Blank-SAP as a negative control (IT-21) were injected bilaterally into the nodose ganglion for selective vagal deafferentation of the upper GI tract of mice.

Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)

Matynia A, Recio BS, Myers Z, Parikh S, Goit RK, Brecha NC, Pérez de Sevilla Müller L (2024) Preservation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in late adult mice: Implications as a potential biomarker for early onset ocular degenerative diseases. Invest Ophthalmol Vis Sci 65(1):28. doi: 10.1167/iovs.65.1.28 PMID: 38224335

Objective: To assess the preservation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in late adult mice and evaluate their potential as biomarkers for early onset ocular degenerative diseases.

Summary: This study investigates the stability of ipRGC morphology and function in mice aged 6 to 12 months, revealing that ipRGCs maintain their dendritic complexity and associated behavioral functions, such as pupillary light reflex and contrast sensitivity, during this period. These findings suggest that the consistent preservation of ipRGCs in late adulthood may serve as a valuable biomarker for early detection of ocular degenerative diseases, including Alzheimer’s, Parkinson’s, and diabetes.

Usage: Whole mount retinas were incubated with Anti-Melanopsin (AB-N39) at 1:1000 for 7 days at 4°C.

Related Products: Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)

Lu S, Gan L, Lu T, Zhang K, Zhang J, Wu X, Han D, Xu C, Liu S, Yang F, Qin W, Wen W (2024) Endosialin in cancer: Expression patterns, mechanistic insights, and therapeutic approaches. Theranostics 14(1):379-391. doi: 10.7150/thno.89495 PMID: 38164138

Objective: To discuss the use of a saporin conjugate to 78Fc, an antibody fragment directed towards endosialin a.k.a. CD248, in the treatment of human sarcomas.

Summary: Endosialin/CD248 is over expressed in cancer and a human single-chain variable fragment -Fc fusion protein was created targeting this receptor, 78Fc. 78Fc was then conjugated to saporin creating an immunotoxin. 78Fc-SAP is discussed as a immunotoxic strategy for the treatment of endosialin-based treatment therapies in cancer.

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

See Also:

• Guo Y et al. Tumour endothelial marker 1/endosialin-mediated targeting of human sarcoma. Eur J Cancer 90:111-121, 2018.

Gong S, Qiu J, Thayumanavan S (2024) Self-assembly of epitope-tagged proteins and antibodies for delivering biologics to antigen presenting cells. J Am Chem Soc 146(1):33-38. 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)

Malley KM, Ruiz AD, Darrow MJ, Danaphongse TT, Shiers S, Ahmad FN, Mota Beltran C, Stanislav BT, Rennaker II RL, Kilgard MP, Hays SA (2023) Neural mechanisms responsible for vagus nerve stimulation-dependent enhancement of somatosensory recovery. SSRN doi: 10.2139/ssrn.4662058

Objective: Optimizing and identifying mechanism of curative action in Vagus Nerve Stimulation therapy on a model of somatosensory deficiency.

Summary: Vagus Nerve Stimulation (VNS) offers promise as a means to treat impairments in somatosensory function after a nerve injury. In a model of chronic sensory loss, VNS of moderate intensity was found to be the most therapeutic. VNS treatment mechanisms were found through models of cholinergic deficits created by 192-IgG-SAP.

Usage: Lesions to the nucleus basalis of rats were made with 192-IgG-SAP [IT-01] (0.375 mg/mL in saline).

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

Bortolotti M, Biscotti F, Zanello A, Polito L, Bolognesi A (2024) Heterophyllin: A new adenia toxic lectin with peculiar biological properties. Toxins 16(1):1. doi: 10.3390/toxins16010001 PMID: 38276525

Objective: Describe the novel type II Ribosome Inactivating Protein, Heterophyllin.

Summary: Heterophyllin, a novel toxic lectin from Adenia heterophylla shows enzymatic and lectin properties of type 2 RIPs. Heterophyllin was able to completely abolish cell viability at nM concentration. The enzymatic, immunological, and biological activities of heterophyllin provide interest in possible pharmacological application.

Usage: Saporin is used as a Type I Ribosome Inactivating Protein to compare it to Heterophyllin, a type II RIP.

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

See Also:

• Bortolotti, M.; Biscotti, F.; Zanello, A.; Bolognesi, A.; Polito, L. New insights on saporin resistance to chemical derivatization with heterobifunctional reagents. Biomedicines 2023, 11, 1214.

Chan A, Tsourkas A (2024) Intracellular protein delivery: Approaches, challenges, and clinical applications. BME Frontiers 5:0035. doi: 10.34133/bmef.0035 PMID: 38282957

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:

• Ancheta LR et al. Saporin as a commercial reagent: its uses and unexpected impacts in the biological sciences-tools from the plant kingdom. Toxins (Basel) 14(3):184, 2022.