References

Chen S (2024) Nanocapsule-based prodrugs for targeted treatment of AIDS-associated non-hodgkin lymphoma. Univ California Thesis.

Objective: To propose a novel nanocapsule based platform that encapsulates the native drugs using various monomers and crosslinkers through free radical polymerization.

Summary: This encapsulation technology modifies the surface properties of the encapsulated drugs, enhancing their penetration into deeper tumor tissues and across the blood-brain barrier (BBB). Moreover, it significantly improves the stability of the drugs in vivo, protecting them from rapid degradation or clearance by the immune system. By adjusting the composition of the monomers and crosslinkers, the surface charge, hydrophobicity, and size of the nanocapsules can be finely tuned to maximize their efficacy in reaching and penetrating the target tissues.

Usage: Conjugation of ch128.1Av (anti-TfR1 IgG3-avidin fusion protein) with biotinylated saporin 6 (b-SO6) to eliminate malignant cells, including NHL malignancies. However, safe systemic delivery of ch128.1Av/b-SO6 is limited by its non-specific toxicity to normal cells expressing TfR1.

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

Thomson AC (2024) Puberty-associated changes in Kiss1r, MC3R, and MC4R in the ewe. West Virginia Univ Thesis.

Objective: To examine kisspeptin receptor (Kiss1r) mRNA expression in gonadotropin releasing hormone (GnRH) neurons and melanocortin 3 and 4 receptor (MC3R/MC4R) expression in kisspeptin neurons across pubertal development.

Summary: Kiss1r expression in GnRH neurons increased with development. In the arcuate nucleus (ARC), the proportion of kisspeptin neurons expressing MC3R, but not MC4R, also rose, though MC3R signal intensity remained unchanged. ARC Kiss1r expression did not vary. Findings support increased GnRH neuron sensitivity to kisspeptin and aMSH as part of the pubertal neurocircuitry.

Usage: Author references prior studies. Deletion of about 75% of KNDy neurons through targeted NKB-SAP (IT-63) injections significantly delayed puberty onset. Reduction of Kiss1r expression in the ARC via targeted injection of a Kisspeptin-SAP (IT-102) conjugate disrupted pulsatile LH release and blocked the LH surge.

Related Products: NKB-SAP (Cat. #IT-63), Kisspeptin-SAP (Cat. #IT-102)

See Also:

• Aerts EG et al. The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep. Biol Reprod 110(2):275-287, 2024.

Kolster MK (2024) Cleavable peptide-triterpene conjugates for improved gene delivery. Univ Berlin Thesis.

Objective: To use SO1861, a saponin triterpene, conjugated to a Saporin-encoding gene to target in vivo mice tumors.

Summary: Targeted nanoplexes containing covalently conjugated SO1861 were prepared by incorporation of a targeting peptide and tested in vivo in an allograft tumor model in mice. Using a suicide gene vector encoding the cytotoxic protein saporin, treatment with targeted SO1861-containing nanoplexes was observed to slow tumor growth and improve survival compared to vehicle control.

Usage: Saporin-nanocomplexes were intravaneuously injected into mice to determine transfection efficiency.

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

Morroni F, Caccamo A (2024) Advances and Challenges in Gene Therapy for Alzheimer’s Disease. J Alzheimers Dis 101(s1):S417-S431. doi: 10.3233/JAD-230783 PMID: 39422937

Objective: Provide an overview of clinical and preclinical studies where gene therapy techniques have been utilized in the context of Alzheimer’s Disease (AD), highlighting their potential as novel therapeutic strategies.

Summary: Gene therapy offers the potential for long-term benefits by providing sustained therapeutic effects. By modifying or replacing faulty genes, it may slow down or halt the progression of AD. Vector-based genetic therapies have demonstrated promising results in mouse models, but face hurdles such as managing risks associated with vectors and delivery methods.

Usage: Rats with cholinergic deficit were induced by intraseptal injection of 192-IgG-SAP (IT-01).

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

See Also:

• Dobryakova YV et al. Intrahippocampal adeno-associated virus-mediated overexpression of nerve growth factor reverses 192IgG-saporin-induced impairments of hippocampal plasticity and behavior. Front Neurosci 15:745050, 2021.

Souza GMPR, Abbott SBG (2024) Loss-of-function of chemoreceptor neurons in the retrotrapezoid nucleus: What have we learned from it?. Respir Physiol Neurobiol 322:104217. doi: 10.1016/j.resp.2024.104217 PMID: 38237884

Objective: To discuss the current definition of chemoreceptor neurons in the retrotrapezoid nucleus (RTN) and describe how this definition has evolved over time.

Summary: Studies offer evidence that RTN neurons are indispensable for the central respiratory chemoreflex in mammals and exert a tonic drive to breathe at rest. Moreover, RTN has an interdependent relationship with oxygen sensing mechanisms for the maintenance of the neural drive to breathe and blood gas homeostasis. Collectively, RTN neurons are a genetically-defined group of putative central respiratory chemoreceptors that generate CO2-dependent drive that supports eupneic breathing and stimulates the hypercapnic ventilatory reflex.

Usage: One widely adopted approach to eliminate RTN neurons utilizes local microinjections of the ribosomal-toxin Saporin conjugated to the analogue of substance-P (SSP-SAP),which results in cell death of neurokinin receptor 1-expressing neurons in a concentration-dependent manner.

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

See Also:

• Nattie EE et al. Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity. J Physiol 544(Pt 2):603-616, 2002.
• Souza GMPR et al. Breathing regulation and blood gas homeostasis after near complete lesions of the retrotrapezoid nucleus in adult rats. J Physiol 596(13):2521-2545, 2018.
• Takakura AC et al. Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats. Exp Physiol 99(3):571-585, 2014.
• Takakura AC et al. Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apneic threshold in rats. J Physiol 586:2975-2991, 2008.

Edwards CM, Guerrero IE, Thompson D, Dolezel T, Rinaman L (2024) An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory. bioRxiv 2024.04.09.588717. doi: 10.1101/2024.04.09.588717 PMID: 38645069

Objective: To investigate the role of a gut vagal afferent-to-central noradrenergic pathway in modulating the retrieval of conditioned passive avoidance memory in rats.

Summary: This study explores how visceral sensory feedback via vagal afferents and central noradrenergic neurons influences passive avoidance memory retrieval. By lesioning specific neural pathways in adult male rats, the researchers demonstrate that disruption of these circuits significantly increased conditioned passive avoidance behavior, suggesting a critical role for these pathways in integrating interoceptive signals with contextual cues to modulate learned avoidance behaviors.

Usage: 250 ng of CCK-SAP (IT-31) was bilaterally injected into the nodose ganglion to selectively lesion gastrointestinal vagal afferents. 80 ng of Anti-DBH-SAP (IT-03) was injected bilaterally into the ventrolateral bed nucleus of the stria terminalis (vlBNST) to selectively lesion noradrenergic inputs to the anterior vlBNST.

Related Products: CCK-SAP (Cat. #IT-31), Anti-DBH-SAP (Cat. #IT-03)

Balukova A, Bokea K, Barber PR, Ameer-Beg SM, MacRobert AJ, Yaghini E (2024) Cellular imaging and time-domain FLIM studies of meso-tetraphenylporphine disulfonate as a photosensitising agent in 2D and 3D models. Int J Mol Sci 25(8):4222. doi: 10.3390/ijms25084222 PMID: 38673807

Objective: To investigate the uptake and subcellular localization of TPPS2a and evaluate the photooxidative mechanism using reactive oxygen species (ROS) and lipid peroxidation probes combined with appropriate ROS scavengers.

Summary: Overall, it can be concluded that the photophysical properties of TPPS2a in cells are not markedly perturbed and that the fluorescence lifetime behavior is consistent with that observed in model systems where both porphyrin monomers and aggregates are present.

Usage: Authors previously studied the PDT and PCI efficacy of TPPS2a in HEY cells in 2D and 3D spheroid models using saporin as the chemotherapeutic agent.

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

See Also:

• Hadi LM, Yaghini E, Stamati K, Loizidou M, MacRobert AJ. (2018) Therapeutic enhancement of a cytotoxic agent using photochemical internalisation in 3D compressed collagen constructs of ovarian cancer. Acta Biomater 81:80-92. doi: 10.1016/j.actbio.2018.09.041 PMID: 30267880
• Mohammad Hadi L, Stamati K, Yaghini E, MacRobert AJ, Loizidou M (2023) Treatment of 3D in vitro tumoroids of ovarian cancer using photochemical internalisation as a drug delivery method. Biomedicines 11(2):572. doi: 10.3390/biomedicines11020572 PMID: 36831108

Kumbhare D, Rajagopal M, Toms J, Freelin A, Weistroffer G, McComb N, Karnam S, Azghadi A, Murnane KS, Baron MS, Holloway KL (2024) Deep brain stimulation of nucleus basalis of meynert improves learning in rat model of dementia. bioRxiv 2024.04.05.588271. doi: 10.1101/2024.04.05.588271 PMID: 38645266

Objective: To assess the effects of varying stimulation patterns and duration on learning in a dementia rat model.

Summary: Deep brain stimulation (DBS) of nucleus basalis of Meynert (NBM) has been considered a potential treatment for dementia, but more study is needed to determine the ideal parameters for NBM stimulation. 192-IgG-SAP (Cat. IT-01) was used to lesion cholinergic neurons of rats creating a rat model of dementia upon which NBM deep brain stimulation could be tested. The desired destruction of neurons was 70-80% cholinergic population lesioned, which through a panel of concentrations was determined to be a 0.50 μg dose. The rat models of dementia were then tested for ideal type and duration of deep brain stimulation to improve operant learning test performance.

Usage: 192-IgG-SAP was bilaterally injected in the NBM in the following amounts: 0.00 (control), 0.15, 0.30, 0.50, and 0.75 μg in 0.5 μl PBS.

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

Riccardi F, Tangredi C, Dal Bo M, Toffoli G (2024) Targeted therapy for multiple myeloma: an overview on CD138-based strategies. Front Oncol 14:1370854. doi: 10.3389/fonc.2024.1370854 PMID: 38655136

Objective: To provide an overview of the most important aspects of multiple myeloma (MM) disease and to investigate the molecular functions of CD138 in physiologic and malignant cell states.

Summary: CD138 has been detected as one of the most important antigens characterizing the surface of MM cells. Although most CD138-targeting strategies have shown promising results in in vitro and/or ex vivo cells and in mouse models, there are still some caveats and limitations that need to be carefully considered, especially in terms of mechanism of action and safety.

Usage: In MM, immunotoxins have been constructed from B-B2 and B-B4 mAbs by coupling them to the plant ribosome inactivating protein saporin (PR-01), resulting in a significant reduction in the number of plasma cells (PCs).

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

See Also:

• Vooijs WC, Post J, Wijdenes J, Schuurman HJ, Bolognesi A, Polito L, et al.Efficacy and toxicity of plasma-cell-reactive monoclonal antibodies B-B2 and B-B4 andtheir immunotoxins.Cancer Immunol Immunother. (1996) 42:319–28.

Wei J, Liu H, Zhou F, Zhang H, Zhang L (2024) The recent research progress in neurobiological characteristics and pain regulation of the cerebrospinal fluid-contacting nucleus. Anesthesiology and Perioperative Science 2(17) doi: 10.1007/s44254-024-00051-9

Objective: To provide novel insights into the investigation of pain regulation within bidirectional regulatory pathway between the brain and cerebrospinal fluid, with a specific focus one elucidating the role of the CSF-contacting nucleus as a bridge structure.

Summary: Studies revealed that the targeted destruction of the CSF-contacting nucleus and reduction in the basic pain threshold were achieved by introducing CB-saporin (SAP) into the lateral ventricle, thereby facilitating the pain behavior response in the pain model.

Related Products: CTB-SAP (Cat. #IT-14)

See Also:

• Liu H et al. Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission. Exp Neurol 261:475-485, 2014.
• Cao J et al. [Targeted damage of the cerebrospinal fluid-contacting nucleus contributes to the pain behavior and the expression of 5-HT and c-Fos in spinal dorsal horn of rats]. Zhongguo Ying Yong Sheng Li Xue Za Zhi 30:218-222, 2014.