saporin

Hua C, Qiu L (2024) Polymersomes for therapeutic protein and peptide delivery: Towards better loading properties. Int J Nanomedicine 19:2317-2340. doi: 10.2147/IJN.S444910 PMID: 38476284

Objective: To highlight the potential of polymersomes as the next-generation therapeutic proteins and peptides carrier and to introduce novel approaches and recent progress to achieve satisfactory encapsulation capability of polymersomes for proteins and peptides.

Summary: With the help of intermolecular interactions, such as electrostatic, lipid–protein, and hydrophobic interactions, the drug loading could be significantly improved. Loading improvement could be attained through innovation of preparation methods, ranging from modified traditional film hydration techniques to the novel phase-guided assembly method.

Usage: Effective inhibition of tumor growth was observed in saporin-loaded polymersomes. Mice treated with this formulation experienced a significant extension in median survival time (50 d) compared to PBS (28 d).

Related Products: Saporin (Cat. #PR-01)

See Also:

• Qiu M, Zhang Z, Wei Y, et al. Small-Sized and Robust Chimaeric Lipopepsomes: a simple and functional platform with high protein loading fortargeted intracellular delivery of protein toxin in vivo.Chem Mater.2018;30(19):6831–6838. doi:10.1021/acs.chemmater.8b02868

Berselli E, Coccolini C, Tosi G, Gokce EH, Oliveira MBPP, Fathi F, Krambeck K, Suoto EB (2024) Therapeutic peptides and proteins: Stabilization challenges and biomedical applications by means of nanodelivery systems. Int J Pept Res Ther 30:15. doi: 10.1007/s10989-024-10592-z

Objective: To discuss the stability problems of proteins and peptides that have driven the scientific community to find in nanotechnology a valid alternative for oral administration of biomolecules.

Summary: Nanoparticles have been proposed to improve the gastrointestinal stability of such macromolecules and, thus, their oral bioavailability. It has also been shown that combining different approaches, such as liposomes and hydrophobic ion pairing and hybrid systems made of polymers and lipids, may lead to synergistic advantages in modifying the release profile and the uptake of peptides/proteins through the gut.

Usage: See Fu et al. (2022). This publication showed an efficient result of a nano-encapsulated protein for cancer therapy. They encapsulate da tetra-guanidinium (TG)-modified saporin into tumor microenvironment (TME) pH-responsive polymeric NP.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Fu E, Li Z (2024) Extracellular vesicles: A new frontier in the theranostics of cardiovascular diseases. iRadiology 2(3):240-259. doi: 10.1002/ird3.77

Chan A (2024) Engineering small protein based inhibitors and biodegraders for cytosolic delivery and targeting of the undruggable proteome. Univ Pennsylvania Thesis.

Objective: Studying the delivery of saporin across the cell membrane encapsulated in lipid nanoparticles.

Summary: Protein payloads, like saporin and others, are given negatively charged regions which create binding sites for cationic lipids to encapsulate the protein. The lipid nanoparticles with saporin or other proteins inside have the potential to interact with many more targets within the cell because they now cross the cell barrier more efficiently.

Usage: Encapsulated Saporin [PR-01] in lipid nanoparticles using anionic polypeptide linkers and using it in vivo (Sun, 2022) and in vitro (Rui, 2019).

Related Products: Saporin (Cat. #PR-01)

See Also:

• Rui, Y. et al. Carboxylated branched poly(β-amino ester) nanoparticles enable robustcytosolic protein delivery and CRISPR-Cas9 gene editing. Sci Adv 5, (2019).
• Sun, Y. et al. Phase-separating peptides for direct cytosolic delivery and redox-activatedrelease of macromolecular therapeutics. Nat Chem 14, 274–283 (2022).

Polito L (2024) Women’s special issue series: Biomedicines. Biomedicines 12(3):471. doi: 10.3390/biomedicines12030471 PMID: 38540085

Summary: Saporin is a single-chain ribosome-inactivating protein (RIP) with low toxicity in cells and animals. When the protein is linked to a carrier that facilitates cellular uptake, the protein can become highly and selectively toxic to the cellular target of the carrier. For this reason, saporin is often used to construct immunotoxins or other hybrid conjugates. The article by Bortolotti et al. examined the effect of the most frequently used heterobifunctional reagents on the saporin molecule, intending to insert a chemical bridge between the toxin and the carrier. The authors evaluated the capability of derivatized saporin to maintain its enzymatic properties, i.e., protein synthesis inhibition, deadenylation of DNA, and its biologic properties, i.e., in vitro cytotoxicity. Therefore, this research can be of interest for constructing saporin-based immuno conjugates when small molecules are considered carriers.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Bolognesi, A.; Bortolotti, M.; Maiello, S.; Battelli, M.G.; Polito, L. Ribosome-Inactivating Proteins from Plants: A Historical Overview. Molecules 2016,21, 1627.
• Polito, L.; Djemil, A.; Bortolotti, M. Plant Toxin-Based Immunotoxins for Cancer Therapy: A Short Overview. Biomedicines 2016,4,12.
• Bortolotti, M.; Biscotti, F.; Zanello, A.; Bolognesi, A.; Polito, L. New Insights on Saporin Resistance to Chemical Derivatization with Heterobifunctional Reagents. Biomedicines 2023,11, 1214.

Wang J, Zhang S, Li Y, Xu Q, Kritzer JA (2024) Investigating the cytosolic delivery of proteins by lipid nanoparticles using the chloroalkane penetration assay. Biochemistry 63(4):512-522. doi: 10.1021/acs.biochem.3c00614 PMID: 38334719

Objective: To investigate bovine serum albumin (BSA) protein encapsulation and release within polylysine/polyglutamate (PLys/PGlu) coacervates.

Summary: The findings emphasize the importance of ingredient addition sequence in coacervate formation and encapsulation rates, attributed to preference contact between oppositely charged proteins and poly(amino acid)s.

Usage: The positively-charged saporin and lysozyme protein exhibited the highest encapsulation efficiency when first combined with PGlu, followed by the addition of PLys in simulations of the coacervate encapsulation of saporin.

Related Products: Saporin (Cat. #PR-01)

Lv X, Martin J, Hoover H, Joshi B, Wilkens M, Ullisch DA, Leibold T, Juchum JS, Revadkar S, Kalinovska B, Keith J, Truby A, Liu G, Sun E, Haserick J, DeGnore J, Conolly J, Hill AVS, Baldoni J, Kensil C, Levey D, Spencer AJ, Gorr G, Findeis M, Tanne A (2024) Chemical and biological characterization of vaccine adjuvant QS-21 produced via plant cell culture. iScience 27(3):109006. doi: 10.1016/j.isci.2024.109006 PMID: 38361610

Objective: To report for the first time successful plant cell culture production of Quillaja saponaria (QS)-21 having structural, chemical, and biological properties similar to the bark-extracted product.

Summary: The data demonstrate that cell culture is a sustainable alternative to natural resources to produce QS-21 as an adjuvant. In this proof-of-concept approach, it’s shown that the chemical, biochemical, and biophysical equivalence of bark extract and cell culture-derived QS-21 translate into conserved biological and adjuvant properties both in vitro and in vivo.

Usage: Pseudo cross-presentation assays (25 ng/mL Saporin).

Related Products: Saporin (Cat. #PR-01)

Lu S, Gan L, Lu T, Zhang K, Zhang J, Wu X, Han D, Xu C, Liu S, Yang F, Qin W, Wen W (2024) Endosialin in cancer: Expression patterns, mechanistic insights, and therapeutic approaches. Theranostics 14(1):379-391. doi: 10.7150/thno.89495 PMID: 38164138

Objective: To discuss the use of a saporin conjugate to 78Fc, an antibody fragment directed towards endosialin a.k.a. CD248, in the treatment of human sarcomas.

Summary: Endosialin/CD248 is over expressed in cancer and a human single-chain variable fragment -Fc fusion protein was created targeting this receptor, 78Fc. 78Fc was then conjugated to saporin creating an immunotoxin. 78Fc-SAP is discussed as a immunotoxic strategy for the treatment of endosialin-based treatment therapies in cancer.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Guo Y et al. Tumour endothelial marker 1/endosialin-mediated targeting of human sarcoma. Eur J Cancer 90:111-121, 2018.

Gong S, Qiu J, Thayumanavan S (2024) Self-assembly of epitope-tagged proteins and antibodies for delivering biologics to antigen presenting cells. J Am Chem Soc 146(1):33-38. 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)

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 PMID: 38276525

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)

See Also:

• Bortolotti, M.; Biscotti, F.; Zanello, A.; Bolognesi, A.; Polito, L. New insights on saporin resistance to chemical derivatization with heterobifunctional reagents. Biomedicines 2023, 11, 1214.

Chan A, Tsourkas A (2024) Intracellular protein delivery: Approaches, challenges, and clinical applications. BME Frontiers 5:0035. doi: 10.34133/bmef.0035 PMID: 38282957

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)

See Also:

• Ancheta LR et al. Saporin as a commercial reagent: its uses and unexpected impacts in the biological sciences-tools from the plant kingdom. Toxins (Basel) 14(3):184, 2022.