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Progressive cancer targeting by programmable aptamer-tethered nanostructures
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)
A bioinspired pseudopeptide-based intracellular delivery platform enhances the cytotoxicity of a ribosome-inactivating protein through multiple death pathways
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)
Enhancing pancreatic cancer chemotherapy through photochemical internalisation
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)
T cell death-associated gene 8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain
Dai SP, Yang CC, Chin Y, Sun WH (2024) T cell death-associated gene 8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain. iScience 27(10):110955. doi: 10.1016/j.isci.2024.110955 PMID: 39381739
Objective: To elucidate how T cell death-associated gene 8 (TDAG8)-mediated signaling modulates neuron activities in a mouse model of chronic constriction injury-induced neuropathic pain.
Summary: TDAG8 participated alone in mechanical allodynia induced by constriction injury. TDAG8-Nav1.8 signaling in small-diameter isolectin B4-positive [IB4(+)] neurons initiate mechanical allodynia; it also modulated substance P release from IB4(-) neurons to facilitate the development of early mechanical allodynia. TDAG8-mediated signaling increased medium-to large-diameter IB4(-) neuron activity to maintain late mechanical allodynia; it also modulated substance P release in soma to reduce satellite glial number and Nav1.7 expression, thus attenuating chronic mechanical allodynia.
Usage: Mice were intrathecally injected with IB4-saporin (IB4-SAP, 0.06 mg/mL) or Saporin (0.06 mg/mL)
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Rational engineering of cytosolic delivery systems for protein therapeutics
Lv J, Liu X, Yin L, Cheng Y (2024) Rational engineering of cytosolic delivery systems for protein therapeutics. Acc Mater Res doi: 10.1021/accountsmr.4c00149
Objective: To summarize recent advances in the rational design of cytosolic protein delivery systems.
Summary: Saporin, a cell membrane-impermeable toxin, kills cancer cells by inhibiting protein synthesis. To fully utilize the therapeutic potential of saporin, the authors developed a series of polymeric carriers to deliver saporin into tumor cells.
Usage: Polymeric carriers were used to deliver saporin into tumor cells
Related Products: Saporin (Cat. #PR-01)
Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss
Keilhoz A, Pathak I, Smith CL, Osman KL, Smith L, Oti G, Golzy M, Mz L, Lever TE, Nichols NL (2024) Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss. Front Neurol 15:1441529. doi: 10.3389/fneur.2024.1441529 PMID: 39296960
Objective: To investigate the effects of a strength endurance tongue exercise program on upper airway structure and function.
Summary: Results showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to rats treated with CTB-SAP and exercise and control rats with/without tongue exercise, which were ameliorated with tongue exercise. Additionally, CTB-SAP treated, sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP treated exercise rats or control rats with/without tongue exercise.
Usage: Intralingual injection of either unconjugated CTB+SAP (20 μg CTB+25 μg SAP) or conjugated CTB-SAP (25 μg of CTB conjugated to SAP).
Related Products: CTB-SAP (Cat. #IT-14), Recombinant Cholera Toxin B (Cat. #PR-14), Saporin (Cat. #PR-01)
Enhancing monoclonal antibodies with natural products: Mechanisms and applications
Gunasekaran M, L S, Premarathna AD, (2024) Enhancing monoclonal antibodies with natural products: Mechanisms and applications. Intelligent Pharmacy doi: 10.1016/j.ipha.2024.09.002
Objective: To investigate the novel application of beta-glucan analogs engineered for enhanced immunomodulatory effects, targeting not only malignant cells but also the tumor microenvironment to optimize mAb penetration.
Summary: By combining plant-based expression systems with synthetic biology tools, creating a hybrid platform that surpasses traditional plant or mammalian systems in both yield and safety. This approach not only reduces production costs but also introduces a scalable method for the rapid adaptation of mAbs in response to emerging pathogens or tumor mutations.
Usage: Combining trastuzumab and cetuximab with the plant-derived toxin saporin (PR-01) resulted in a significant increase in cytotoxicity against tumor cells. This approach, especially when paired with plant glycosides, promotes the release of toxins into the cytoplasm, resulting in total cell death in select cancer cell types.
Related Products: Saporin (Cat. #PR-01)
Plant-derived extracellular vesicles: a synergetic combination of a drug delivery system and a source of natural bioactive compounds
Langellotto MD, Rassu G, Serri C, Demartis S, Giunchedi P, Gavini E (2024) Plant-derived extracellular vesicles: a synergetic combination of a drug delivery system and a source of natural bioactive compounds. Springer Nature 11(3) doi: 10.1007/s13346-024-01698-4
Objective: This review intends to provide adequate tools for studying and developing drug delivery systems based on plant-derived extracellular vesicles (EVs).
Summary: Freeze-drying could be useful for preserving plant-derived exosomes at higher temperatures without affecting their size, morphology or other parameters. Still, it may reduce protein activity, as reported by Noguchi and coworkers, who observed a diminished biological activity of protein saporin after its encapsulation in EVs and freeze-drying.
Related Products: Saporin (Cat. #PR-01)
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A cocktail of engineered chimeric antibodies targeting the central nervous system produces a broad-spectrum therapeutic effect for symptomatic rabies
Zhao L, Ren Z, Wang C, Wang H, Wu Q, Hou Q, Qi X, He W, Zhang X, Wan J , Zhoui M, Fu Z (2024) A cocktail of engineered chimeric antibodies targeting the central nervous system produces a broad-spectrum therapeutic effect for symptomatic rabies. Research Square preprint. doi: 10.21203/rs.3.rs-4838561/v1
Objective: To construct and assess four chimeric human-mouse antibodies with high neutralizing activity and affinity against rabies virus (RABV), further identifying their targeted antigenic epitopes as I, II, and IV.
Summary: Results showed that combined treatment of RABV-infected mice with three SynB1-antibodies targeting different epitopes could reduce clinical symptoms and increase survival ratio to 80%. Collectively, the non-invasive brain delivery method based on hybrid antibody-conjugated cell-penetrating peptides offers a promising strategy for the effective treatment of broad-spectrum symptomatic rabies.
Usage: Saporin was suggested as a payload for SynB1 antibodies based on researchers who investigated the use of THR peptides targeting transferrin receptor protein 1 (TFR1) conjugated with drugs for the treatment of Alzheimer’s disease, APOE peptides attached to Saporin (PR-01) to target low-density lipoprotein receptor (LDLR) for glioma therapy, and the TGN peptide-Saporin, which has been studied in the field of epilepsy.
Related Products: Saporin (Cat. #PR-01)
See Also:
- Daniels-Wells TR et al. Insights into the mechanism of cell death induced by saporin delivered into cancer cells by an antibody fusion protein targeting the transferrin receptor 1. Toxicol In Vitro 27(1):220-231, 2013.
- Branco F et al. Peptide-hitchhiking for the development of nanosystems in glioblastoma. ACS Nano 18(26):16359-16394, 2024.
- Thankachan S et al. Ventrolateral periaquaductal gray (vlPAG): Key area for REM sleep propensity. Neuroscience 2008 Abstracts 586.3/SS36, 2008. Society for Neuroscience, Washington, DC
Characterization of MAP c21873-1 as a new counter-selectable marker for unmarked genetic modification of Pichia pastoris
Liu M, Zhou S, Cao Y, Yang K, Xiao Y, Wang W (2024) Characterization of MAP c21873-1 as a new counter-selectable marker for unmarked genetic modification of Pichia pastoris. Microb Cell Fact 23(1):224. doi: 10.1186/s12934-024-02496-w PMID: 39118053
Objective: To establish a new counter-selectable marker-based strategy for seamless modification with high efficiency and low toxicity.
Summary: Development of MAP c21873-1 as a novel counter-selectable marker which could perform efficient gene knock-in by site-directed HR.
Usage: MazF, c21873-1, c23467 and twenty-four RIPs were selected to construct a phylogenetic tree to investigate their relationships in the evolutionary history. The phylogenetic analysis demonstrates that c21873-1 and c23467 are closely relative to type I RIPs such as PAP-S and saporin (PR-01).
Related Products: Saporin (Cat. #PR-01)
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