Herrerias A, Oliverio A, Dvorácskó S, Thyagarajan A, Chedester L, Liu J, Cinar R, Iyer MR, Kunos G, Godlewski G (2025) CB1 receptors on a subset of vagal afferent neurons modulate voluntary ethanol intake in mice. Mol Psychiatry doi: 10.1038/s41380-025-03266-9 PMID: 40975751
Kolahdouzan M, Ghazisaeidi S, Tu Y, Muley M, Gambeta E, Salter M (2025) Meningeal macrophages mask incision pain sensitization in male rats. Mol Pain doi: 10.1177/17448069251383593
Objective: To investigate whether CD206+macrophages in the meninges play a role in regulating nociception and pain hypersensitivity.
Summary: The results indicate that while CD206+ meningeal macrophages do not regulate basal nociception in naïve rats, they mask mechanical hypersensitivity in male rats after skin incision injury. Thus, we conclude that in a sex-dependent manner, CD206+ meningeal macrophages prevent the spread of pain hypersensitivity after a minor injury.
Usage: Rats were injected intrathecally (30 μl) with saline, CD206-Saporin (20 μg mannose-receptor antibody and 7 μg of Streptavidin-ZAP in 30 μl), or Rabbit-IgG-Saporin (control).
Shang Y, Gan X, Dang Y, Liu J, Liu P (2025) The physiological and pathological mechanisms of LIN2, LIN7, LIN10 and their tripartite complex. J Cell Mol Med 29(15):e70794. doi: 10.1111/jcmm.70794 PMID: 40801824
Objective: To furnish a robust theoretical foundation for the prospective utilization of polarity proteins and their complex as cancer markers and therapeutic targets.
Summary: Authors have found that LIN2, LIN7, and LIN10, as well as their complexes, play important roles in the establishment and maintenance of apical-basal polarity. They are also involved in two physiological processes: synaptic transmission and receptor localization. Additionally, LIN2, LIN7, and LIN10 are linked to the pathological processes of type 2 diabetes mellitus and cardiovascular diseases. Meanwhile, they regulate the proliferation, apoptosis, and metastasis of cancer cells through various pathways.
Usage: The PDZ domain of LIN2 can target binding to CD98, a negative prognostic marker for human glioblastoma cells. Constructing a chimera of the PDZ domain of LIN2 with the ribosome-inactivating protein Saporin (PR-01) and enhancing the activity of this chimera as the number of PDZ domains increases can effectively increase cytotoxicity and apoptosis in human glioblastoma cells, GL15 and U87.
Yuan M, Zhang L, Zhu H, Xie M (2025) Alteration of BDNF and noradrenergic markers in locus coeruleus in a mouse model of cancer-induced bone pain. PLoS One 20(8):e0330207. doi: 10.1371/journal.pone.0330207 PMID: 40811566
Objective: To examine the expression and localization of BDNF and NE neuron-specific proteins in the locus coeruleus (LC) of mice with cancer-induced bone pain (CIBP).
Summary: CIBP mice exhibited enhanced neuronal activity in the LC, upregulation of noradrenergic markers, and BDNF/TrkB-mediated modulation of noradrenergic neurons. Concurrently, inhibitory signalling was attenuated in the spinal dorsal horn (SDH).
Usage: Selective ablation of noradrenergic neurons via intracerebroventricular anti-DBH-SAP (IT-03) administration reduces mechanical and cold allodynia, suggesting that LC-spinal cord pathway activity is critical for pain modulation.
Park S, Lu GL, Zheng YC, Davison EK, Li Y (2025) Nanoparticle-based delivery strategies for combating drug resistance in cancer therapeutics. Cancers (Basel) 17(16):2628. doi: 10.3390/cancers17162628 PMID: 40867257
Objective: To explore how nanoparticle-based drug delivery systems can address the challenge of resistance to chemotherapy and targeted therapy by improving drug accumulation in tumors, enhancing targeting specificity, and enabling controlled or stimulus-responsive drug release.
Summary: Nanoparticle-based drug delivery strategies offer a promising and multifaceted approach to overcoming multidrug resistance in cancer therapy. Nanocarriers can address many limitations and challenges associated with conventional chemotherapy by enhancing the intracellular drug accumulation at tumor sites, bypassing efflux transporters, facilitating targeted delivery, and enabling in vivo gene modulation.
Usage: Lipid-saporin nanoparticles were utilized to bypass efflux transporters via the co-delivery of anticancer drugs with ABC transporters, leading to an increase in intracellular drug concentrations and the re-sensitization of drug-resistant cancer cells to chemotherapy.
Pandala N, De Melo Haefeli L, Lang M, Stone EM, Mullins RF, Tucker BA, Han IC (2025) Development of a targeted choroidal injury model for the study of retinal degenerations and therapeutic cell replacement. bioRxiv 2025.07.29.667466. doi: 10.1101/2025.07.29.667466
Objective: To report a new targeted choroidal injury model using saporin conjugates and compare them to models of systemic sodium iodate administration.
Summary: Suprachoroidal administration of Anti-CD38-SAP or Anti-CD105-SAP resulted in severe choroidal vascular injury localized to the injection site, without damage to adjacent choroidal vasculature, progressive injury over time, or development of choroidal neovascularization. By contrast, sodium iodate treated animals had rapid, diffuse choroidal loss which progressed throughout the study time points, with fatal systemic side effects at the highest (75 mg/kg) dose.
Usage: Anti-CD38-SAP (IT-96) or Anti-CD105-SAP (IT-80) were diluted in sterile PBS at a concentration of 0.05 μg/μl. To induce selective choroidal cell injury, 10μl of saporin conjugate solution was delivered via suprachoroidal injection.
Kofoed C, Erkalo G, Tay NES, Ye X, Lin Y, Muir TW (2025) Programmable protein ligation on cell surfaces. Nature 10.1038/s41586-025-09287-2. doi: 10.1038/s41586-025-09287-2 PMID: 40739351
Lee H, Hor CC, Horwitz LR, Xiong A, Su XY, Soden DR, Yang S, Cai W, Zhang W, Li C, Radcliff C, Dinh A, Fung TLR, Rovcanin I, Pipe KP, Xu XZS, Duan B (2025) A dedicated skin-to-brain circuit for cool sensation in mice. Nat Commun 16(1):6731. doi: 10.1038/s41467-025-61562-y PMID: 40721582
Objective: To investigate the functional contributions of specific spinal dorsal horn neuron subtypes to cold and pain sensation using targeted ablation and optogenetic tools.
Summary: The study identifies Calb1+ spinal neurons as essential mediators of cool sensation in mice. Behavioral and physiological responses following targeted ablation reveal distinct sensory processing roles for various neuronal subtypes.
Usage: Bombesin-SAP (IT-40), or control conjugate Blank-SAP (IT-21), was administered intrathecally at a dose of 400 ng in 10 μL sterile saline to ablate GRPR+ spinal neurons and assess their role in sensory behavior.
Nazmuddin M, Stammes MA, Klink PC, Vernes MK, Bakker J, Langermans JAM, van Laar T, Philippens IHCHM (2025) Stereotactic lesioning of cholinergic cells by injection of ME20.4 Saporin in the nucleus basalis of Meynert in a rhesus monkey (Macaca mulatta). J Neuropathol Exp Neurol nlaf081. doi: 10.1093/jnen/nlaf081 PMID: 40673943
Objective: To describe a procedure to inject ME20.4-SAP, an immunotoxin that specifically binds to and depletes cholinergic neurons stereotactically into the nucleus basalis of Meynert (NBM) of a rhesus monkey (Macaca mulatta).
Summary: A digital non-human primate brain atlas was co-registered to the brain of the monkey. A custom-designed cranial chamber was also implanted to the skull to guide the injection. The effects of the ME20.4-SAP injections were evaluated in vivo with PET-CT using [18F]-FEOBV as a radiotracer. This approach yielded reliable spatial accuracy and successful delivery of ME20.4-SAP into the NBM. This saporin-mediated selective destruction of cholinergic neurons in the NBM, using MRI-guidance and a cranial chamber, offers a promising method to study the pathophysiology of NBM degeneration and possible therapeutic interventions.
Usage: The first dose was chosen based on previous NBM lesioning works in common marmosets where infusing 1.4 μg ME20.4-SAP (Cat. #IT-15, in a concentration of 0.20 μg/μl) into each side of the NBM produced partial NBM depletion. At the second injection session, 5 μg ME20.4-SAP (in 0.5 μg/μl solution) was administered into each NBM side.
Noble EE, Harris RBS (2025) Leptin in the VMH contributes to the initial overconsumption of palatable diets by rats. Am J Physiol Endocrinol Metab 329(1):E1-E17. doi: 10.1152/ajpendo.00090.2025 PMID: 40418155
Objective: To determine whether leptin receptor–expressing neurons in the ventromedial hypothalamus (VMH) contribute to the initial overconsumption of a high-fat diet in rats.
Summary: Ablation of VMH leptin receptor–expressing neurons using Leptin-SAP prevented the early hyperphagic response to a high-fat diet in male rats but had no long-term impact on energy intake, body weight, or glucose clearance. These findings suggest VMH leptin signaling plays a key role in initiating, but not maintaining, diet-induced hyperphagia.
Usage: Leptin-SAP (IT-47) or Blank-SAP (IT-21) was stereotaxically injected into the VMH of male and female rats (20 ng in 80 nL) to ablate leptin receptor–expressing neurons. This targeted lesion confirmed the role of VMH leptin signaling in mediating early-phase overeating in response to a high-fat diet.
