References

Mohammadi F, Zahraee H, Zibadi F, Khoshbin Z, Ramezani M, Alibolandi M, Abnous K, Taghdisi SM (2024) Progressive cancer targeting by programmable aptamer-tethered nanostructures. MedComm (2020) 5(11):e775. doi: 10.1002/mco2.775 PMID: 39434968

Objective: This review focuses on the significance of different aptamer-assembled nanoconstructs as multifunctional nucleic acid oligomeric nanoskeletons in efficient drug delivery.

Summary: Saporin was attached to a βCD-conjugated aptamer. After treating HeLa cells with the circular bivalent aptamer (Cb-Apt)‒saporin complex, cell viability decreased by 20%, whereas mono-apt‒saporin showed no significant toxicity. The Cb-Apt‒βCD complex effectively improved the intracellular delivery of saporin.

Usage: 1:50 molar ratio (nanostructure:saporin).

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

Jiang H, Cui H, Chen M, Li F, Shen X, Guo CJ, Hoekel GE, Zhu Y, Han L, Wu K, Holtzman MJ, Liu Q (2024) Divergent sensory pathways of sneezing and coughing. Cell 187(21):5981-5997. doi: 10.1016/j.cell.2024.08.009 PMID: 39243765

Objective: To study the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing.

Summary: Sneezing and coughing are frequently associated with allergies and respiratory viral infections and it’s assumed both involve common sensory receptors and neurotransmission mechanisms. The author’s work show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3−) mediates sneezing. Although this same population innervates the trachea, it does not mediate coughing, and instead, a distinct sensory population (somatostatin SST) mediates coughing but not sneezing. NMB-SAP was used to ablate neruomedin B (NMB) receptor expressing and nucleus tractus solitarius (NTS) neurons. Deletion of these neurons did not affect the coughing responses to Ly344864 and IL-31 (agonists to SST neurons) suggesting that NMB-sensitive NTS neurons do not mediate coughing.

Usage: Neuronal ablation by SST-saporin and NMB-saporin. SST-saporin was made by mixing biotin-labeled somatostatin and Streptavidin-ZAP (IT-27) at a 1:1 molar ratio at room temperature for 20 minutes. SST-Saporin (10 μM, 50 nL), NMB-saporin (#IT-70; 50 ng in 50 nL) or Blank-SAP (#IT-21; 10 μM in 50 nL or 50 ng in 50 nL) was injected into the NTS region.

Related Products: Streptavidin-ZAP (Cat. #IT-27), NMB-SAP (Cat. #IT-70), Blank-SAP (Cat. #IT-21)

Limonta P, Chiaramonte R, Casati L (2024) Unveiling the dynamic interplay between cancer stem cells and the tumor microenvironment in melanoma: Implications for novel therapeutic strategies. Cancers (Basel) 16(16):2861. doi: 10.3390/cancers16162861 PMID: 39199632

Objective: To review the bidirectional communication between melanoma cancer stem cells (CSCs) and the tumor microenvironment, highlighting its role in drug resistance and tumor relapse.

Summary: Melanoma CSCs evade immune surveillance and recruit immune cells with immunosuppressive and tumor-promoting properties, establishing a supportive microenvironment. They also transfer stemness and aggressive traits to neighboring non-CSCs, driving tumor progression and metastasis. Targeting these interactions may offer novel therapeutic strategies for combating melanoma.

Usage: This review publication highlights the usage of Anti-CD271-SAP and CD133-SAP in previous publications.

Related Products: ME20.4-SAP (Cat. #IT-15), Anti-CD133-SAP (Cat. #IT-82), Saporin (Cat. #PR-01)

See Also:

• Ngo M et al. Antibody therapy targeting CD47 and CD271 effectively suppresses melanoma metastasis in patient-derived xenografts. Cell Rep 16:1701-1716, 2016.
• Bostad M et al. Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization – A minimally invasive cancer stem cell-targeting strategy. J Control Release 206:37-48, 2015.

Coutinho EA, Esparza LA, Steffen PH, Liaw R, Bolleddu S, Kauffman AS (2024) Selective depletion of kisspeptin neurons in the hypothalamic arcuate nucleus in early juvenile life reduces pubertal LH secretion and delays puberty onset in mice. FASEB J 28(19):e70078. doi: 10.1096/fj.202401696R PMID: 39377760

Objective: To investigate the specific kisspeptin population timing pubertal onset.

Summary: This study teases apart the contributions of different kisspeptin neural populations to the control of puberty onset, demonstrating that a majority of KNDy neurons in the arcuate nucleus are necessary for the proper timing of puberty in both sexes.

Usage: See also these studies where ~70% of ARC kisspeptin (KNDy) neurons were selectively ablated in rats using NKB-SAP (IT-63).

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

See Also:

• Mittelman-Smith MA et al. Arcuate kisspeptin/neurokinin b/dynorphin (KNDy) neurons mediate the estrogen suppression of gonadotropin secretion and body weight. Endocrinology 153(6):2800-2812 , 2012 .
• Helena C et al. KNDy neurons modulate the magnitude of the steroid-induced luteinizing hormone surges in ovariectomized rats. Endocrinology 156:4200-4213, 2015.
• Mittelman-Smith M et al. Ablation of KNDy neurons results in hypogonadotropic hypogonadism and amplifies the steroid-induced LH surge in female rats. Endocrinology 157:2015-2027, 2016.
• Campideli-Santana AC et al. Partial loss of arcuate kisspeptin neurons in female rats stimulates luteinizing hormone and decreases prolactin secretion induced by estradiol. J Neuroendocrinol 34(11):e13204, 2022.

Lusk S, Moushey AM, Li A, Ray R (2024) Exaggerated postnatal surge of orexin neurons and the effects of elimination of excess orexin on blood pressure and exaggerated chemoreflex in spontaneously hypertensive rats. Front Physiol 15:1341649. doi: 10.3389/fphys.2024.1341649 PMID: 39469444

Objective: To investigate whether an increase in postnatal neurogenesis of orexin (OX) neurons in spontaneously hypertensive rats (SHRs) precedes and contributes to elevated mean arterial pressure (MAP) and heightened responses to elevated CO2 (hypercapnia) during development.

Summary: Postnatal increase in OX neurons may be essential for the development of higher MAP and an exaggerated chemoreflex (the body’s response to CO2) in SHRs. Targeting the overactive OX system could provide a potential therapeutic strategy during the early stages of hypertension development.

Usage: Orexin-SAP (0.5 μL, 90 ng/μL) was injected into the hypothalamus to eliminate excess OX neurons and study their effect on elevated MAP and exaggerated chemoreflex responses in adult SHRs.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Doucette L, Turnbill V, Carlin K, Cavanagh A, Sollinger B, Kuter N, Flock DL, Robinson S, Chavez-Valdez R, Jantzie L, Martin LJ, Northington FJ (2024) Neocortical cholinergic pathology after neonatal brain injury is increased by Alzheimer’s disease-related genes in mice. Neurobiol Dis 200:106629. doi: 10.1016/j.nbd.2024.106629 PMID: 39111704

Objective: Authors hypothesized that neocortical damage caused by neonatal Hypoxic-ischemic (HI) in mice is ushered by persistent cholinergic innervation and interneuron (IN) pathology that correlates with cognitive outcome and is exacerbated by genes linked to Alzheimer’s disease.

Summary: Simple ChAT+axonal swellings were present in all sham and HI groups; Tg mice had more than their nTg counterparts, but HI did not affect the number of axonal swellings. In contrast, complex ChAT+neuritic clusters (NC) occurred only in Tg mice. The abundance of ChAT+ clusters in specific regions correlated with decreased Visual discrimination. This finding aligns with data that a highly specific cholinergic immunotoxin (mu p75-SAP) in the APP/PS1 mouse model worsens cognitive impairment, and the cognitive impairment appears earlier

Related Products: mu p75-SAP (Cat. #IT-16)

See Also:

• Ramos-Rodriguez JJ et al. Rapid beta-amyloid deposition and cognitive impairment after cholinergic denervation in app/ps1 mice. J Neuropathol Exp Neurol 72(4):272-285, 2013.

Morrison G, Henry N, Kopytynski M, Chen R (2024) A bioinspired pseudopeptide-based intracellular delivery platform enhances the cytotoxicity of a ribosome-inactivating protein through multiple death pathways. Biomater Sci 12(19):5010-5022. doi: 10.1039/d4bm00600c PMID: 39177215

Objective: To overcome Saporin’s poor plasma membrane permeability.

Summary: To overcome this barrier, authors used a bioinspired intracellular delivery platform based on the pH-responsive pseudo peptide, poly (L-lysine isophthalamide) grafted with L-phenylalanine at a stoichiometric molar percentage of 50% (PP50). PP50 was co-incubated with saporin (PP50/saporin) in a mildly acidic pH environment to aid intracellular delivery and increase saporin’s therapeutic potential. It was shown that PP50 is a potential intracellular delivery platform for the internalization of protein therapeutic.

Usage: PP50/saporin formulations were prepared with D-PBS solutions at pH 6.5 containing PP50 at a specific concentration of 0.025, 0.1, 0.2, 0.5 or 5 mg mL−1 and Saporin (PR-01) at varying concentrations.

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

O’Sullivan JA, Youngblood BA, Schleimer RP, Bochner BS (2024) Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases. Semin Immunol 69:101799. doi: 10.1016/j.smim.2023.101799 PMID: 37413923

Objective: To review a subset of Siglecs and their various endogenous or synthetic sialoside ligands that regulate eosinophil and mast cell function and survival.

Summary: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are vertebrate glycan-binding cell-surface proteins. Many Siglecs mediate cellular inhibitory activity and are of interest as part of a strategy to therapeutically lessen unwanted cellular responses. Human eosinophils and mast cells express overlapping but distinct patterns of Siglecs, and certain Siglecs have become the focus of novel therapies for allergic and other eosinophil and mast cell-related diseases.

Usage: Saporin in conjunction with CD22 glycomimetic ligand BPCNeuAc leads to cells death induction in a ligand-dependent manner on B-lymphoma cells (Collins et al.). Incubation with anti-Siglec-8 monoclonal antibody conjugated to saporin led to the death of malignant mast cells and eosinophils (O’Sullivan et al.)

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

See Also:

• Collins BE, Blixt O, Han S, Duong B, Li H, Nathan JK, Bovin N, Paulson JC (2006) High-affinity ligand probes of CD22 overcome the threshold set by cis ligands to allow for binding, endocytosis, and killing of B cells. J Immunol 177(5):2994-3003. doi: 10.4049/jimmunol.177.5.2994 PMID: 16920935
• 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.

la Fleur SE, Blancas-Velazquez AS, Stenvers DJ, Kalsbeek A (2024) Circadian influences on feeding behavior. Nauropharmacology 256:110007. doi: 10.1016/j.neuropharm.2024.110007 PMID: 38795953

Objective: To review the effect of deletion of different clock genes on feeding behavior.

Summary: The most prominent effect on feeding behavior has been observed in Clock mutants, where as deletion of Bmal1 and Per1/2 only disrupts the day-night rhythm, but not overall intake. Damaging leptin-sensitive cells within the ARC using saporin-leptin injections (reducing the number of POMC and AgRP cells) induced a-rhythmicity in feeding behavior when animals were held either in a light-dark rhythm or continuous darkness, providing evidence that leptin-sensitive cells of the ARC are important for circadian feeding rhythmicity.

Related Products: Leptin-SAP (Cat. #IT-47)

See Also:

• Li AJ et al. Leptin-sensitive neurons in the arcuate nuclei contribute to endogenous feeding rhythms. Am J Physiol Regul Integr Comp Physiol 302(11):R1313-26, 2012.

Rosado M, Mahamed I, Garcia-Sampedro A, MacRoberts S, Selbo P, Pereira S, Acedo P (2024) Enhancing pancreatic cancer chemotherapy through photochemical internalisation. Cancer Res 84 (17_Supplement_2):A027. doi: 10.1158/1538-7445.PANCREATIC24-A027

Objective: The aim is to use the technique called Photochemical Internalisation (PCI), a light-triggered intracellular drug delivery method which combines low dose PhotodynamicTherapy (PDT) with chemotherapy, to induce efficient cytosolic delivery of therapeutic compounds to their specific subcellular targets.

Summary: Observation of minimal cytotoxicity induced by saporin, gemcitabine or TPPS2a+ light monotherapies. However, PCI synergistically enhanced saporin and gemcitabine cytotoxicity (p<0.001) using very low concentrations in all tumor models. Findings demonstrate the potential of PCI to enhance the efficacy of cancer chemotherapy for pancreatic cancer using lower doses than in monotherapy and open a new window for future translational studies.

Usage: Saporin was used as monotherapy or in combination with a light-activated photosensitizer.

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