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Self-assembly of epitope-tagged proteins and antibodies for delivering biologics to antigen presenting cells
Gong S, Qiu J, Thayumanavan S (2023) Self-assembly of epitope-tagged proteins and antibodies for delivering biologics to antigen presenting cells. J Am Chem Soc doi: 10.1021/jacs.3c09334 PMID: 38147631
Objective: To describe a simple self-assembly strategy for generating artificial immune complexes.
Summary: The built-in recognition domains in the antibody, viz. the Fab and Fc domains, are judiciously leveraged for cargo conjugation to generate the nanoassembly and macrophage targeting, respectively. A responsive linker is engineered into the nanoassembly for releasing the protein cargo inside the macrophages while ensuring stability during delivery.
Usage: Cytotoxicity assay to measure cell death with targeted saporin.
Related Products: Saporin (Cat. #PR-01)
Intracellular protein delivery: Approaches, challenges, and clinical applications
Chan A, Tsourkas A (2024) Intracellular protein delivery: Approaches, challenges, and clinical applications. BME Frontiers doi: 10.34133/bmef.0035
Objective: To review progress made towards achieving cytosolic delivery of recombinant proteins and possible strategies to enable proteins to cross cell membranes.
Summary: Drug delivery researchers have worked to deliver saporin into tumor cells in the hopes of producing potent next-generation cancer therapeutics. Cationic, anionic, and zwitterionic versions of poly(β-amino ester) have been developed for delivery of saporin. Chemically-modified saporin can be encapsulated by cationic LNPs for in vivo tumor inhibition. Saporin has been used as a model cargo protein for in vivo delivery via fluoropolymer nanoparticles for successful tumor growth inhibition.
Related Products: Saporin (Cat. #PR-01)
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Exploring the potential of nanogels: From drug carriers to radiopharmaceutical agents
Kubeil M, Suzuki Y, Casulli MA, Kamal R, Hashimoto T, Bachmann M, Hayashita T, Stephan H (2023) Exploring the potential of nanogels: From drug carriers to radiopharmaceutical agents. Adv Healthc Mater e2301404. doi: 10.1002/adhm.202301404 PMID: 37717209
Summary: This review provides a brief overview of current developments of nanogels in the fields of drug delivery, therapeutic applications, tissue engineering and sensor systems. The authors described one development using saporin. Mimicking the function of molecular chaperones, Kawasaki et al. created magnetic in vivo protein transport nanogels with encapsulated iron oxide nanoparticles. The nanogels also contained saporin, which was rapidly released by an exchange reaction with serum protein. The evaluation using an oral cancer model revealed a reduction in tumor volume and suppression of tumor regrowth, with no change in body weight.
Related Products: Saporin (Cat. #PR-01)
See Also:
- Kawasaki R et al. (2021) Magnetically navigated protein transduction in vivo using iron oxide-nanogel chaperone hybrid. Adv Healthc Mater 10(9):e2001988. doi: 10.1002/adhm.202001988 PMID: 33694289
Emerging non-viral vectors for gene delivery
Wang C, Pan C, Yong H, Wang F, Bo T, Zhao Y, Ma B, He W, Li M (2023) Emerging non-viral vectors for gene delivery. J Nanobiotechnology 21(1):272. doi: 10.1186/s12951-023-02044-5 PMID: 37592351
Summary: This review describes the fastest-growing and efficient non-viral gene delivery vectors that include liposomes and lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). One group designed and synthesized HPAEs with positive and negative charges to deliver saporin. Another group performed cell experiments that demonstrated that a boronic acid-grafted dendrimer vector had good delivery ability for saporin.
Related Products: Saporin (Cat. #PR-01)
The gut-brain axis mediates bacterial driven modulation of reward signaling
Kim JS, Williams KC, Kirkland RA, Schade R, Freeman KG, Cawthon CR, Rautmann AW, Smith JM, Edwards GL, Glenn TC, Holmes PV, de Lartigue G, de La Serre CB (2023) The gut-brain axis mediates bacterial driven modulation of reward signaling. Mol Metab 26:101764. doi: 10.1016/j.molmet.2023.101764 PMID: 37380023
Objective: To investigate the role of gut microbiota and vagal signaling in modulating brain dopamine reward pathways and appetitive feeding behavior.
Summary: The study found that high-fat diet and transfer of high-fat microbiota to germ-free rats reduced dopamine signaling and motivated feeding behavior compared to chow-fed and low-fat microbiota groups. Vagal deafferentation restored dopamine signaling and feeding motivation in high-fat microbiota rats, indicating gut bacteria signals that dampen reward are vagally mediated.
Usage: Animals were injected bilaterally into the nodose ganglion with either Saporin or CCK-SAP. A pulled glass micropipette containing either CCK-SAP (240 ng/ml in 0.1 M phosphate buffer) or SAP alone was inserted under the sheath of the cervical vagus and into the NG, the injection was done with a pressure-injector into two sites (one proximal and one distal, total volume, 1 µl).
Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)
Intracellular delivery of therapeutic proteins. New advancements and future directions
Porello I, Cellesi F (2023) Intracellular delivery of therapeutic proteins. New advancements and future directions. Front Bioeng Biotechnol 11:1211798. doi: 10.3389/fbioe.2023.1211798 PMID: 37304137
Objective: To provide a brief overview of the current methods for intracellular protein delivery to mammalian cells.
Summary: The field of intracellular protein delivery is still a relatively young area of research and further advancements in this field will require the integration of chemistry, materials science, formulation science, nanomedicine, and biomedical engineering.
Usage: Saporin was referenced as a molecule with the advantage of being able to block the synthesis of proteins in cells.
Related Products: Saporin (Cat. #PR-01)
RIPpore: A novel host-derived method for the identification of ricin intoxication through oxford nanopore direct RNA sequencing
Ryan Y, Harrison A, Trivett H, Hartley C, David J, Clark GC, Hiscox JA (2022) RIPpore: A novel host-derived method for the identification of ricin intoxication through oxford nanopore direct RNA sequencing. Toxins (Basel) 14(7):470. doi: 10.3390/toxins14070470
Objective: The Depurination event could be detected using Oxford Nanopore Technologies (ONT) direct RNA sequencing, detecting a change in charge in the ricin loop.
Summary: Collectively, this work highlights the potential for ONT and direct RNA sequencing to detect and quantify depurination events caused by ribosome-inactivating proteins such as ricin.
Usage: Saporin was added as described by Rust et al., at 100 nM [22] for 24 h.
Related Products: Saporin (Cat. #PR-01)
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Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs.
Li Y, Ye Z, Yang H, Xu Q (2022) Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs. Acta Pharm Sin B 12(6):2624-2639. doi: 10.1016/j.apsb.2022.04.013
Objective: To highlight the recent progress in combinatorial lipid nanoparticles (LNPs) with novel structures and properties for the delivery of small- and macromolecular therapeutics.
Summary: The administration of protein/LNP negatively impacted reproduction in rats, including sperm production, estrous cyclicity and testicular and ovarian morphology, without causing any significant side effects. This non-surgical approach can be developed into a safe and convenient strategy for controlling the overproduction of pet and wildlife.
Usage: Intravenous administration of saporin loaded LNPs
Related Products: Saporin (Cat. #PR-01)
Maintenance mechanism of nociplastic pain in males
McDonough KE (2022) Maintenance mechanism of nociplastic pain in males. University of Texas Medical Branch Thesis.
Objective: The objective of this dissertation is to elucidate the sex-specific mechanisms underlying the transition to and maintenance of a nociplastic pain state using animal models.
Summary: This PhD dissertation investigates the mechanisms underlying the transition from acute to chronic nociplastic pain using murine models. The study finds that in males, spinal microglial activation driven by GABAergic disinhibition allows normally innocuous stimulation to induce a transition to nociplastic pain maintained by spinal microglia and proinflammatory cytokines.
Usage: Intrathecal injection of Saporin or Mac-1-SAP at 8.85 μM.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)
Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats.
Xu L, Füredi N, Lutter C, Geenen B, Pétervári E, Balaskó M, Dénes Á, Kovács KJ, Gaszner B, Kozicz T (2022) Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats. Neuropharmacology 205:108898. doi: 10.1016/j.neuropharm.2021.108898
Objective: To show that leptin bound to neurons of the Edinger-Westphal nucleus (EWcp) stimulated STAT3 phosphorylation and increases urocortin 1 (Ucn1)-production in a time-dependent manner.
Summary: EWcp/LepRb/Ucn1 neurons respond to leptin signaling as well as control white adipose tissue size and fat metabolism without altering food intake.
Usage: Ablation of EWcp leptin receptor (LepRb) positive neurons with leptin-saporin. Either unconjugated saporin (53 ng in 80 nl MQ, or Leptin-SAP (90 ng in 80 nl MQ, was injected into the rat midbrain.
Related Products: Leptin-SAP (Cat. #IT-47), Saporin (Cat. #PR-01)