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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)
Heterophyllin: A new adenia toxic lectin with peculiar biological properties
Bortolotti M, Biscotti F, Zanello A, Polito L, Bolognesi A (2024) Heterophyllin: A new adenia toxic lectin with peculiar biological properties. Toxins 16(1):1. doi: 10.3390/toxins16010001
Objective: Describe the novel type II Ribosome Inactivating Protein, Heterophyllin.
Summary: Heterophyllin, a novel toxic lectin from Adenia heterophylla shows enzymatic and lectin properties of type 2 RIPs. Heterophyllin was able to completely abolish cell viability at nM concentration. The enzymatic, immunological, and biological activities of heterophyllin provide interest in possible pharmacological application.
Usage: Saporin is used as a Type I Ribosome Inactivating Protein to compare it to Heterophyllin, a type II RIP.
Related Products: Saporin (Cat. #PR-01)
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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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The specificity landscape of bacterial ribonuclease P
Chamberlain AR, Huynh L, Huang W, Taylor DJ, Harris ME (2023) The specificity landscape of bacterial ribonuclease P. J Biol Chem 300(1):105498. doi: 10.1016/j.jbc.2023.105498 PMID: 38013087
Objective: Review of the specificity of ribonucleoprotein RNase P in binding different types of RNA.
Summary: Ribonucelase P is involved in the RNA metabolism pathways. By studying the rate at which it combines with different types of RNA under different conditions, like concentration and competition with different enzymes, a model describing its specificity to different RNA motifs can be developed.
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)
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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)
Cell-Penetrating Peptide-Based Delivery of Macromolecular Drugs: Development, Strategies, and Progress
Sun Z, Huang J, Fishelson Z, Wang C, Zhang S (2023) Cell-Penetrating Peptide-Based Delivery of Macromolecular Drugs: Development, Strategies, and Progress. Biomedicines 11(7):1971.
Objective: Review the development process of cell penetrating peptides and summarize the composition and classification of the penetrating peptide-based delivery systems, cellular uptake mechanisms, influencing factors, and biological barriers.
Summary: Delivery of macromolecular drugs (like saporin) with a cell penetrating peptide can be an effective way to create bioavailability. The principle underlying these approaches is to briefly destroy the cell membrane so that macromolecular drugs can enter the cell, after which the cell membrane is repaired and can restore cell homeostasis. Compared to other methods, the use of Cell Penetrating Peptides causes less damage to the cell membrane and is more effective and safe offering itself as a useful tool for macromolecular drug delivery.
Usage: Saporin as a conjugate to cell penetrating peptides. Nakase (2016) uses Saporin as a part of an extracellular vesicle conjugated with octaarginine, a cell penetrating peptide.
Related Products: Saporin (Cat. #PR-01)
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Dynamically crosslinked nanocapsules for the efficient and serum-resistant cytosolic protein delivery
Yang Q, Liu N, Zhao Z, Liu X, Yin L (2023) Dynamically crosslinked nanocapsules for the efficient and serum-resistant cytosolic protein delivery. Nano Research doi: 10.1007/s12274-023-5978-2
Objective: Improve protein delivery with the synthesis of epigallocatechin gallate/low-molecular-weight polyethylenimine/2-acetylphenylboric acid (EPP)-protein nano-capsules.
Summary: A protein delivery strategy was created through the crosslinking of various markers on the protein surface, hence forming the EPP-protein nano-capsules. The EPP-protein nano-capsule allowed for acid-triggered dissociation of EPP-protein nano-capsules in the endolysosomes, which triggered efficient intracellular release of the native proteins. Acid dissociation showed high efficiency and universality for diversities of proteins with different molecular weights and isoelectric points, including enzymes, toxins, antibodies, and CRISPR-Cas9 ribonucleoprotein.
Usage: Delivered into in vivo 4T1 tumors in mice (PBS, saporin, or EPP-saporin nano-capsules were i.v. injected (0.5 mg saporin/kg) on day 0, 2, 4, and 6) and in vitro HeLa cells (seeded with 0, 0.05, 0.1, 0.2, 0.5, 1, and 2 μg/mL concentrations of Saporin or EPP-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)