targeted-toxins

Loftén A, Cadeddu D, Danielsson K, Stomberg R, Adermark L, Söderpalm B, Ericson M (2024) Reduced alcohol consumption following ablation of cholinergic interneurons in the nucleus accumbens of wistar rats. Addict Biol 30(2):e70022. doi: 10.1111/adb.70022 PMID: 39936333

Objective: The aim of this study was to explore the functional role of accumbal Cholinergic interneurons (CIN) in alcohol-related behavior.

Summary: Rats with depleted CIN consumed significantly less alcohol than sham-treated controls. No differences in sucrose preference, motor activity, water intake or weight gain were noted between treatment groups, suggesting that the ablation selectively affected alcohol-related behavior. In conclusion, this study further supports a role for accumbal CIN in regulating alcohol-consummatory behavior.

Usage: Ablation of CIN was induced by local administration of Anti-ChAT-SAP (Cat #IT-42) bilaterally into the nucleus accumbens of male Wistar rats. Dose: 0.5 and 0.75 μg/ul.

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Su Y, Xu J, Zhu Z, Chin J, Xu L, Yu H, Nudell V, Dash B, Moya EA, Ye L, Nammerjahn A, Sun X (2024) Brainstem DBH+ neurons control chronic allergen-induced airway hyperreactivity. bioRxiv 2023.02.04.527145. doi: 10.1101/2023.02.04.527145

Summary: The authors show that a single population of Dbh+ neurons in the nucleus of the solitary tract (nTS) of the brainstem, and downstream neurons in the nucleus ambiguous (NA), are both necessary and sufficient for chronic allergen-induced airway hyperreactivity. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted hyperreactivity. This opens the possibility of targeted neural modulation as an approach to control refractory allergen- induced airway constriction.

Usage: Anti-DBH-SAP (IT-03) was injected stereotactically into both sides of the nTS of wild-type mice (42 ng/200 nL). Blank-SAP (IT-21) was used as control.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Blank-SAP (Cat. #IT-21)

Yelamali AR, Chendamarai E, Ritchey JK, Rettig MP, DiPersio JF, Persaud SP (2024) Streptavidin-drug conjugates streamline optimization of antibody-based conditioning for hematopoietic stem cell transplantation. bioRxiv 2024.02.12.579199. doi: 10.1101/2024.02.12.579199 PMID: 38405731

Objective: Use biotinylated CD45.2 antibodies conjugated to Streptavidin to target hematopoietic stem cells (HSCs) for HSC transplantation.

Summary: Hematopoietic stem cell transplantation offers a promising alternative to standard cancer treatments. Using Click Chemistry, different toxic payloads were attached to streptavidin and observed.

Usage: 75 micrograms of CD45.2 delivered to HSCs deriving from B6 mice.

Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)

Abdolvahab MH, Karimi P, Mohajeri N, Abedini M, Zare H (2024) Targeted drug delivery using nanobodies to deliver effective molecules to breast cancer cells: The most attractive application of nanobodies. Cancer Cell Int 24(1):67. doi: 10.1186/s12935-024-03259-8 PMID: 38341580

Objective: Using nanobodies to deliver saporin to breast cancer cells.

Summary: Through the binding of saporin to a nanobody, a fragment of an antibody, breast cancer cells that over-express Her2 can be targeted and eliminated. Binding of saporin in nanoparticles to 11A4 nanobody (anti-HER2 receptor) showed dose-dependent cytotoxicity against SK-BR-3 cells when tested. Photochemical internalization of saporin loaded nanoparticles also demonstrated dose-dependent cytotoxicty in SK-BR-3 breast cancer cells.

Related Products: Trastuzumab (Anti-HER2)-SAP (Cat. #IT-95)

See Also:

• Martínez-Jothar L, Beztsinna N, van Nostrum CF, Hennink WE, Oliveira S (2019) Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination with Photochemical Internalization. Mol Pharm 16(4):1633-1647. doi: 10.1021/acs.molpharmaceut.8b01318 PMID: 30817164

Aerts EG, Griesgraber MJ, Shuping SL, Bowdridge EC, Hardy SL, Goodman RL, Nestor CC, Hileman SM (2024) 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. doi: 10.1093/biolre/ioad147 PMID: 37930247

Objective: To investigate the role of NKB-SAP (NK3-SAP) in the arcuate nucleus on the timing of puberty, the LH surge, and the response to the NK3R agonist senktide in female sheep.

Summary: This study explores how the ablation of NK3R-containing neurons in the arcuate nucleus affects puberty onset and reproductive hormone dynamics in female sheep. The findings demonstrate that NK3-SAP injections significantly delay puberty, reduce the amplitude of the LH surge, and alter the response to senktide, underscoring the critical role of NK3R-containing neurons in reproductive function.

Usage: Prepubertal ewes received 1 μL (0.7 μg) of NKB-SAP (NK3-SAP) [IT-63] or Blank-SAP (IT-21) injections aimed at the arcuate (ARC) nucleus to ablate neurons expressing NK3R.

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

Martínez-Gardeazabal J, Moreno-Rodríguez M, Llorente-Ovejero A, González de San Román E, Lombardero L, Bengoetxea de Tena I, Sustacha J, Matute C (2024) Cell lipotypes localization in brain by mass spectrometry imaging. bioRxiv doi: 10.1101/2024.02.02.578599

Objective: Characterizing the type of different central nervous system cells via mass spectrometry of their component lipids.

Summary: Different varieties of cells in the central nervous system perform different functions and, as a consequence, have different compositions. Using purified rat cell cultures of neurons, astrocytes, oligodendrocytes, microglia, and choroid plexus cells, a model was constructed to identify the localization of any brain cell through mass spectrum imaging of the lipid composition.

Usage: Injected 192-IgG-SAP (130 ng/µl) into the nucleus basalis magnocellularis (nbM) of rats.

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

Schwarz KG, Pereyra KV, Diaz-Jara E, Vicencio SC, Del Rio R (2024) Brainstem C1 neurons mediate heart failure decompensation and mortality during acute salt loading. Cardiovascular Research doi: 10.1093/cvr/cvae261 PMID: 39775485

Objective: To test whether rostral ventrolateral medulla (RVLM) C1 neurons drive cardiorespiratory decompensation, and ultimately lead to sudden death in heart failure (HF) rats.

Summary: The results strongly suggest that RVLM C1 neurons contribute to acute HF decompensation during salt loading by a mechanism encompassing further increases in sympathetic outflow and hypoxia-related breathing disorder.

Usage: Bilateral injections of anti-dopamine-β-hydroxylase conjugated with saporin toxin (Anti-DBH-SAP; 7.5 ng/100 nl of sterile saline solution) were delivered to the RVLM-C1 region using the stereotaxic coordinates.

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

Björklund A, Barker RA (2024) The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease. Brain awae026. doi: 10.1093/brain/awae026 PMID: 38279949

Objective: Review the use of cholinergic cell replacement as a potential therapeutic strategy in Parkinson’s Disease (PD) and how rodent models of PD-like cognitive decline can be used by analyzing rodent and primate studies.

Summary: Although therapies targeting the cholinergic system have so far been focused mainly on patients with Alzheimer´s disease, PD with dementia may be a more relevant condition. In PD with dementia the Basal Forebrain system undergoes progressive degeneration, and the magnitude of cholinergic cell loss has been shown to correlate with the level of cognitive impairment. Thus, cell therapy aimed to replace the lost basal forebrain cholinergic neurons represents an interesting strategy to combat some of the major cognitive impairments in patients with PD dementia.

Usage: Rats were given 192-IgG-SAP (IT-01), 0.2-0.4 μg, delivered as a single 0.3-1.0 μl injection into either the substantia innominate/nucleus basalis of Meynert (SI/NBM) or the medial septum/ventral diagonal band (MS/VDB).

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

Bernabe CS, Caliman IF, de Abreu ARR, Molosh AI, Truitt WA, Shekhar A, Johnson PL (2024) Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses. Transl Psychiatry 14(1):60. doi: 10.1038/s41398-024-02769-3 PMID: 38272876

Objective: To investigate the role of serotonergic inputs from the raphe nuclei to the perifornical hypothalamic area (PFA) in regulating panic and fear responses.

Summary: This study identifies a novel serotonergic system projecting to the PFA that inhibits innate panic and conditioned fear responses. The findings suggest that serotonergic inputs from the lateral wings of the dorsal and median raphe nuclei to the PFA represent a panic/fear-off circuit, which could also play a role in modulating reward behaviors.

Usage: Each rat (Adult Sprague-Dawley; 300–350 g) received two bilateral microinjections per site (100 nl each, 1 μM in ACSF) of either Anti-SERT-SAP (IT23) or the control Mouse IgG-SAP (IT-18) via an injector that was connected to bilateral guide-cannulas implanted into the PFA.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)

Fulton S, Horn CC, Zhang C (2024) Characterizing a new tool to manipulate area postrema GLP1R+ neurons across species. Physiol Behav 114474. doi: 10.1016/j.physbeh.2024.114474 PMID: 38272107

Objective: Characterize the ligand exenatide conjugated to saporin as a tool to ablate GLP1 receptor-expressing cells from human, mice, and shrews, a small animal model capable of emesis (vomiting).

Summary: Nausea is a distressing sensation that is a common side effect of many medications. Nausea and emesis are among the top adverse side effects of glucagon-like peptide-1 (GLP1) receptor (GLP1R) agonists-based medications to treat type 2 diabetes and obesity. The area postrema is a brain structure that mediates nausea effects. The authors provide characterization of Ex4-SAP (GLP-1-SAP) to specifically ablate GLP1R-expressing HEK293T cells in vitro and in area postrema neurons in mice and house musk shrews in vivo.

Usage: C57BL-6J mice were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 200 ng/ul, in a total of 400 nl at a rate of 2 nl/second. Musk shrews were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 500 ng/ul, in a total of 200 nl at a rate of 2 nl/second.

Related Products: Ex4-SAP (GLP-1-SAP) (Cat. #IT-90), Blank-Streptavidin-SAP (Cat. #IT-27B)