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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. doi: 10.3390/biomedicines11071971 PMID: 37509610
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 (2024) Dynamically crosslinked nanocapsules for the efficient and serum-resistant cytosolic protein delivery. Nano Research 17:1760-1771. 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 ribosome-inactivating proteins MAP30 and Momordin inhibit SARS-CoV-2
Watts NR, Eren E, Palmer I, Huang PL, Huang PL, Shoemaker RH, Lee-Huang S, Wingfield PT (2023) The ribosome-inactivating proteins MAP30 and Momordin inhibit SARS-CoV-2. PLoS One 18(6):e0286370. doi: 10.1371/journal.pone.0286370 PMID: 37384752
Summary: Saporin is mentioned in the discussion of RIPs and their usage as antivirals.
Related Products: Saporin (Cat. #PR-01)
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A comparison of cellular uptake mechanisms, delivery efficacy, and intracellular fate between liposomes and extracellular vesicles
Gandek TB, van der Koog L, Nagelkerke A (2023) A Comparison of Cellular Uptake Mechanisms, Delivery Efficacy, and Intracellular Fate Between Liposomes and Extracellular Vesicles. Adv Healthc Mater 12(25):e2300319. doi: 10.1002/adhm.202300319 PMID: 37384827
Objective: Using peptide-functionalized extracellular vesicles (EVs), filled with saporin, to increase cytotoxicity over normal biological EVs.
Summary: Extracellular vesicles were used as a means to deliver saporin to HeLa and CHO-K1 cells. Octaarginine peptides (R8 peptides) are seeded on the surface of the EVs which enhanced the macropinocytotic uptake and internalization efficiency as compared to unmodified EVs.
Usage: Saporin was packaged in extracellular vesicles with R8 pepetides and treated on HeLa (Nakase, 2016) and CHO-K1 cells (Nakase, 2017).
Related Products: Saporin (Cat. #PR-01)
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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)
Self-assembled nanogels consisting of cholesterol-bearing polysaccharides and their applications in medicine
Antonia-Nancy H, Matsumoto M, Tahara Y (2023) Self-assembled nanogels consisting of cholesterol-bearing polysaccharides and their applications in medicine. (eds. Dr. Chukwuebuka Emmanuel Umeyor, Dr. Emmanuel Uronnachi and Dr. Pratik Kakade). In: Hydrogels and Nanogels – Applications in Medicine doi: 10.5772/intechopen.1001981
Objective: Using iron oxide-containing nano-gels containing saporin to magnetically guide the targeting of saporin.
Summary: Nanogels containing inorganics are an emerging tool to direct the targeting of drugs within the body. Saporin was bound in a cholesterol-bearing pullulan nanogel with particles of iron oxide was magnetically steered through the chaperoning gel to treat a model of oral cancer.
Usage: Using Saporin bound to magnetic nanogel to target a model of oral cancer. See Also: Saporin usage form these two papers: KawasakiR, SasakiY, KatagiriK, MukaiS-A, SawadaS-I, AkiyoshiK. Magnetically guided protein transduction by hybrid Nanogel chaperones with iron oxide nanoparticles. Angewandte Chemie, International Edition. 2016;55:11377-11381.DOI:10.1002/anie.201602577 KawasakiR, SasakiY, NishimuraT, KatagiriK, MoritaK-I, SekineY, etal. Magnetically navigated protein transduction In vivo using iron oxide-Nanogel chaperone hybrid. Advanced Healthcare Materials. 2021;10:2001988.DOI:10.1002/adhm.202001988
Related Products: Saporin (Cat. #PR-01)
Direct cytosolic delivery of proteins and CRISPR-Cas9 genome editing by gemini amphiphiles via non-endocytic translocation pathways
Le Z, Pan Q, He A, Liu H, Shi Y, Liu L, Liu Z, Ping Y, Chen Y (2023) Direct cytosolic delivery of proteins and CRISPR-Cas9 genome editing by gemini amphiphiles via non-endocytic translocation pathways. ACS Cent Sci 9(7):1313-1326. doi: 10.1021/acscentsci.3c00207 PMID: 37521791
Objective: Create a library composed of 150 gemini amphiphiles (GAs), a molecule with polar and nonpolar regions, to identify means to facilitate delivery of saporin across the cell membrane.
Summary: The gemini amphiphiles studied differ in the spacing of functional groups, hydrophobicity and sterics. A Cas9 ribonucleoprotein conjugated to saporin showed highest efficacy for internalization. HeLa cells were used to study the efffects of this found gemini-amphiphile conjugated to saporin.
Usage: A1I2-1R2C18 [a gemini ampiphile] conjugated to saporin and treated against HeLa cells at 0.0625, 0.125, 0.25, 0.5, 1μg/mL for 4 hours and then assessed for cell viability.
Functional l-arginine derivative as an efficient vector for intracellular protein delivery for potential cancer therapy
He X, Qu Y, Xiong S, Jiang Z, Tang Y, Yan F, Deng Y, Sun Y (2023) Functional l-arginine derivative as an efficient vector for intracellular protein delivery for potential cancer therapy. J Funct Biomater 14(6):301. doi: 10.3390/jfb14060301 PMID: 37367265
Objective: To address the instability of the 9-fluorenylmethyloxycarbonyl (Fmoc) group in aqueous medium.
Summary: The Fmoc ligand neighboring arginine was substituted for dibenzocyclooctyne (DBCO) with a similar structure to Fmoc to obtain stable DBCO-functionalized L-arginine derivative (DR). DBCO-functionalized L-arginine derivative represents an excellent potential vector for protein-based cancer therapy.
Usage: The synthesized DR monomer was first dissolved in sterilized ultrapure water with a concentration of 1 mg/mL, then mixed with protein solution at a weight ratio of 5:1 for saporin (DR:SA) for 10 min at room temperature. Saporin was added at 110μg/mL to MDA-MB-231 cells (DR: SA-FITC: HA,w:w:w, 5:1:25)
Related Products: 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)
Addressing the key issue: Antigen-specific targeting of B cells in autoimmune diseases
Holborough-Kerkvliet MD, Kroos S, van de Wetering R, Toes REM (2023) Addressing the key issue: Antigen-specific targeting of B cells in autoimmune diseases. Immunol Lett 259:37-45. doi: 10.1016/j.imlet.2023.05.005 PMID: 37209914
Objective: Using cyclic citrullinated peptide (CCP) conjugated to CNBz and saporin to eliminate autoreactive B cells, as a treatment for rheumatoid arthritis (RA).
Summary: Joint damage in the body creates cyclic citrullinated peptide (CCP) which is a marker of Rheumatoid arthritis (RA). The CCP active site that autoantibodies target is blocked with CNBz and the whole complex is conjugated with saporin allowing cytotoxicity directed towards autoreactive B cells, a damaging element of RA, without being reactive with CCP-targeted autoantibodies.
Related Products: Saporin (Cat. #PR-01)
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