saporin

Shirsat SD, Londhe PV, Gaikwad AP, Rizwan M, Laha SS, Khot VM, Achal C, Tabish TA, Thorat ND (2024) Endosomal escape in magnetic nanostructures: Recent advances and future perspectives. Materials Today Advances 22:100484. doi: 10.1016/j.mtadv.2024.100484

Objective: To investigate the use of magnetic nanoparticles (MNPs) as functional nano-objects to enhance the therapeutic effects by disrupting or rupturing the endocytic vesicles in terms of endosomal escape.

Summary: When MNPs are functionalized for cancer therapy, the endosomal escape agent should break the endosomal membrane when it fuses with lysosomes, i.e. late endosomes, which are highly acidic and comprised of large amounts of hydrolytic enzymes, which additionally contribute to cytotoxic effects. However, when MNPs are used for gene delivery, endosomal release from early endosomes should be desirable because it is less toxic than late endosomes, thus increasing the biocompatibility and promoting healthy growth and gene expression in targeted cells.

Usage: Saporin is mentioned as an endosomal escape agent.

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

See Also:

• Vago R et al. Saporin and ricin A chain follow different intracellular routes to enter the cytosol of intoxicated cells. FEBS J 272(19):4983-4995, 2005.

Smakosz A, Matkowski A, Nawrot-Hadzik I (2024) Phytochemistry and biological activities of agrostemma genus-a review. Plants (Basel) 13(12):1673. doi: 10.3390/plants13121673 PMID: 38931105

Objective: In this review, papers focused on the chemical composition and bioactivity of the two accepted species of the Agrostemma genus were examined.

Summary: A vast amount of data exists about the cytotoxicity of Agrostemma and other Caryophyllaceae plants. However, there are huge differences between models and experimental procedures, resulting in difficulty in reaching reasonable conclusions as to whether or not these properties would indeed be pharmacologically relevant for anti-cancer therapies.

Usage: Saporin inhibits HIV-1 reverse transcriptase, HIV-1 protease, and HIV-1 integrase (Au et al.). Saponins isolated from a related plant—Gypsophila sp. —enhanced the cytotoxicity of saporin 100,000-fold. This demonstrates how important the synergy of RIPs and saponins is in the toxicity of plants from Caryophyllaceae (Hebestreit et al.)

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

See Also:

• Au, T.K.; Collins, R.A.; Lam, T.L.; Ng, T.B.; Fong, W.P.; Wan, D.C.C. The Plant Ribosome Inactivating Proteins Luffin and SaporinAre Potent Inhibitors of HIV-1 Integrase.FEBS Lett.2000,471, 169–172.
• Hebestreit, P.; Weng, A.; Bachran, C.; Fuchs, H.; Melzig, M.F. Enhancement of Cytotoxicity of Lectins by Saponinum Album.Toxicon2006,47, 330–335.

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

Objective: To delve into the evolving landscape of extracellular vesicles (EVs), uncovering their diagnostic and therapeutic prospects and emphasizing their growing importance in shaping the future of cardiovascular theranostics

Summary: The ability of EVs to act as conduits of molecular information, orchestrate cellular responses, and influence the behaviors of recipient cells will allow precision interventions in cardiovascular disease (CVD) treatment. The continuous refinement of biomaterial‐based strategies and innovative delivery methods will improve the precision and efficacy of EV interventions, establishing a solid foundation for their experimental application. Enhanced cellular uptake and cytosolic release of exosomes has been achieved by combining a pH‐sensitive fusogenic peptide and cationic lipids. This method facilitates the efficient delivery of encapsulated molecules, including 70kD adextran and the ribosome‐inactivating protein named saporin.

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

See Also:

• NakaseI, FutakiS. Combined treatment with a pH‐sensitive fusogenic peptide and cationic lipids achieves enhanced cytosolic delivery of exosomes. SciRep.2015;5(1):10112. https://doi.org/10.1038/srep10112

Stockdale JN (2024) Pollen-specific expression of ecori restriction endonuclease for bioconfinement in panicum virgatum l. Univ Tennessee Thesis.

Objective: In this study, pollen-specific promoters controlling the expression of the EcoRI endonuclease, interrupted by a catalase intron, were evaluated for efficacy to produce sterile pollen.

Summary: The TaPSG719, PvPS1, Osg6B, OsRTS, and Zm13 promoters were assessed for pollen-specific expression patterns, none of which have previously been characterized in switchgrass. The effectiveness of pollen-targeted EcoRI expression to produce sterile pollen was not determined. However, this study identified the Zm13 and PvPS1 promoters as strong candidates for male-specific gene expression and provided valuable insights for the design and production of genetically engineered switchgrass

Usage: In the Genesafe prototype system, saporin was used as a sterility gene to inhibit protein synthesis and cause seed sterility when expressed in plant cells. The system relied on hybridizing two parent plants (P1 and P2), with saporin expression controlled by a late embryo-specific promoter (LEA4A or LEA14 from cotton) and repressed by a blocker sequence. After hybridization, a stimulus would trigger Cre/loxP recombinase to excise the blocker, enabling saporin expression in the next generation. However, in tobacco trials, seed sterility was not achieved due to inefficient promoter activity and low saporin production.

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

Schulze FJ, Asadian-Birjand M, Pradela M, Niesler N, Nagal G, Fuchs H, (2024) A cleavable peptide adapter augments the activity of targeted toxins in combination with the glycosidic endosomal escape enhancer SO1861. BMC Biotechnol 24(1):24. doi: 10.1186/s12896-024-00854-5 PMID: 38685061

Objective: To examine whether the addition of the molecular adapter, that consists of a cell penetrating peptide and two cleavable peptides, further augments the endosomal escape enhancement of the glycosylated triterpenoid SO1861, which has shown up to more than 1000‑fold enhancement in the past.

Summary: Introducing the peptide adapter into the targeted toxin led to an about 12‑fold enhancement in the cytotoxicity on target cells while SO1861 caused a 430‑fold increase. However, the combination of adapter and glycosylated triterpenoid resulted in a more than 4300‑fold enhancement and in addition to a 51‑fold gain in specificity.

Usage: When inserting the adapter A2 between the ribosome-inactivating protein, saporin (PR-01) and the targeting moiety EGF (Saporin-A2-EGF), an improved anti-cancer effect in mice with EGFR-positive tumors and simultaneously lesser side effects were observed in comparison to Saporin-EGF.

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

Kolster MK (2024) Cleavable peptide-triterpene conjugates for improved gene delivery. Univ Berlin Thesis.

Objective: To use SO1861, a saponin triterpene, conjugated to a Saporin-encoding gene to target in vivo mice tumors.

Summary: Targeted nanoplexes containing covalently conjugated SO1861 were prepared by incorporation of a targeting peptide and tested in vivo in an allograft tumor model in mice. Using a suicide gene vector encoding the cytotoxic protein saporin, treatment with targeted SO1861-containing nanoplexes was observed to slow tumor growth and improve survival compared to vehicle control.

Usage: Saporin-nanocomplexes were intravaneuously injected into mice to determine transfection efficiency.

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)

Balukova A, Bokea K, Barber PR, Ameer-Beg SM, MacRobert AJ, Yaghini E (2024) Cellular imaging and time-domain FLIM studies of meso-tetraphenylporphine disulfonate as a photosensitising agent in 2D and 3D models. Int J Mol Sci 25(8):4222. doi: 10.3390/ijms25084222 PMID: 38673807

Objective: To investigate the uptake and subcellular localization of TPPS2a and evaluate the photooxidative mechanism using reactive oxygen species (ROS) and lipid peroxidation probes combined with appropriate ROS scavengers.

Summary: Overall, it can be concluded that the photophysical properties of TPPS2a in cells are not markedly perturbed and that the fluorescence lifetime behavior is consistent with that observed in model systems where both porphyrin monomers and aggregates are present.

Usage: Authors previously studied the PDT and PCI efficacy of TPPS2a in HEY cells in 2D and 3D spheroid models using saporin as the chemotherapeutic agent.

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

See Also:

• Hadi LM, Yaghini E, Stamati K, Loizidou M, MacRobert AJ. (2018) Therapeutic enhancement of a cytotoxic agent using photochemical internalisation in 3D compressed collagen constructs of ovarian cancer. Acta Biomater 81:80-92. doi: 10.1016/j.actbio.2018.09.041 PMID: 30267880
• Mohammad Hadi L, Stamati K, Yaghini E, MacRobert AJ, Loizidou M (2023) Treatment of 3D in vitro tumoroids of ovarian cancer using photochemical internalisation as a drug delivery method. Biomedicines 11(2):572. doi: 10.3390/biomedicines11020572 PMID: 36831108

Riccardi F, Tangredi C, Dal Bo M, Toffoli G (2024) Targeted therapy for multiple myeloma: an overview on CD138-based strategies. Front Oncol 14:1370854. doi: 10.3389/fonc.2024.1370854 PMID: 38655136

Objective: To provide an overview of the most important aspects of multiple myeloma (MM) disease and to investigate the molecular functions of CD138 in physiologic and malignant cell states.

Summary: CD138 has been detected as one of the most important antigens characterizing the surface of MM cells. Although most CD138-targeting strategies have shown promising results in in vitro and/or ex vivo cells and in mouse models, there are still some caveats and limitations that need to be carefully considered, especially in terms of mechanism of action and safety.

Usage: In MM, immunotoxins have been constructed from B-B2 and B-B4 mAbs by coupling them to the plant ribosome inactivating protein saporin (PR-01), resulting in a significant reduction in the number of plasma cells (PCs).

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

See Also:

• Vooijs WC, Post J, Wijdenes J, Schuurman HJ, Bolognesi A, Polito L, et al.Efficacy and toxicity of plasma-cell-reactive monoclonal antibodies B-B2 and B-B4 andtheir immunotoxins.Cancer Immunol Immunother. (1996) 42:319–28.

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)