saporin

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)

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)

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)

Chen S (2024) Nanocapsule-based prodrugs for targeted treatment of AIDS-associated non-hodgkin lymphoma. Univ California Thesis.

Objective: To propose a novel nanocapsule based platform that encapsulates the native drugs using various monomers and crosslinkers through free radical polymerization.

Summary: This encapsulation technology modifies the surface properties of the encapsulated drugs, enhancing their penetration into deeper tumor tissues and across the blood-brain barrier (BBB). Moreover, it significantly improves the stability of the drugs in vivo, protecting them from rapid degradation or clearance by the immune system. By adjusting the composition of the monomers and crosslinkers, the surface charge, hydrophobicity, and size of the nanocapsules can be finely tuned to maximize their efficacy in reaching and penetrating the target tissues.

Usage: Conjugation of ch128.1Av (anti-TfR1 IgG3-avidin fusion protein) with biotinylated saporin 6 (b-SO6) to eliminate malignant cells, including NHL malignancies. However, safe systemic delivery of ch128.1Av/b-SO6 is limited by its non-specific toxicity to normal cells expressing TfR1.

Related Products: MonoBiotin-ZAP (Cat. #BT-ZAP)

Nattkemper LA, Kim BS, Yap QV, Hoon MA, Mishra SK, Yosipovitch G (2024) Increased systemic levels of centrally acting b-type natriuretic peptide are associated with chronic itch of different types. J Invest Dermatol S0022-202X(24)00197-0. doi: 10.1016/j.jid.2024.02.026 PMID: 38522572

Objective: Examines plasma BNP levels and N-terminal pro-BNP levels in patients with differing types of chronic itch to see whether BNP and N-terminal pro-BNP levels can correlate with itch severity.

Summary: Plasma BNP and N-terminal pro-BNP levels of all patients with itch correlated with itch numerical rating scale, particularly for patients with chronic pruritus of unknown origin. Based on this clinical observation, this study further showed that increasing pathophysiological levels of BNP in mice by intravenous or osmotic pump induced significant scratching. In addition, BNP-SAP lesions to mice determined that BNP acts centrally by activating the natriuretic peptide receptor A in the dorsal horn of the spinal cord.

Usage: BNP-SAP was injected intrathecally (5 µg in 10 µL). One week later an itch agonist agent, ivBNP, was injected and itching was measured over an hour.

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

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 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)