saporin

Zeynalzadeh E, Khodadadi E, Khodadadi E, Ahmadian Z, Kazeminava F, Rasoulzadehzali M, Samadi Kafil H (2024) Navigating the neurological frontier: Macromolecular marvels in overcoming blood-brain barrier challenges for advanced drug delivery. Heliyon 10(15):e35562. doi: 10.1016/j.heliyon.2024.e35562 PMID: 39170552

Objective: To understand how nanoparticles interact with the blood-brain barrier.

Summary: Enhancing the bioavailability of nano formulations at the intended site is critical. The use of surface ligands that target brain endothelial cell receptors may improve BBB penetration. In summary, nanomaterials offer vast potential in the realm of brain-targeted therapies, from early detection to effective treatment.

Usage: Saporin (PR-01) was cited for protein toxin delivery as a therepeutic agent for BBB penetration.

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See Also:

• Y.Jiang,W.Yang,J.Zhang,F.Meng,Z.Zhong, Protein toxin chaperoned by LRP-1-targeted virus-mimicking vesicles induces high-efficiency glioblastoma therapy in vivo,Adv.Mater.30(2018)1800316.

Wang Y, Zou R, Zhou Y, Zheng Y, Peng C, Liu Y, Tan H, Fu Q, Ding M (2024) Unraveling mechanisms of protein encapsulation and release in coacervates via molecular dynamics and machine learning. Chem Sci doi: 10.1039/D4SC03061C

Objective: To investigate bovine serum albumin (BSA) protein encapsulation and release within polylysine/polyglutamate (PLys/PGlu) coacervates and to conduct simulations of the coacervate encapsulation of saporin, lysozyme, actin, and EGFP proteins in the LG, GL and SIM sequence to explore the potential extension of the ingredient addition sequence effect to other proteins.

Summary: 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. Notably, coacervates composed of b-sheet poly(amino acid)s demonstrate greater BSA encapsulation efficiency due to their reduced entropy and flexibility. The positively charged saporin and lysozyme protein exhibited the highest encapsulation efficiency when first combined with PGlu, followed by the addition of PLys.

Usage: The authors conducted simulations of the coacervate encapsulation of saporin (PR-01).

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Xia L, Luo L, Liu J, Liu L, Han H, Xia R, Guo L, Xie J, Tang L (2024) A glycoprotein-based surface-enhanced raman spectroscopy–lateral flow assay method for abrin and ricin detection. Toxins (Basel) 16(7):312. doi: 10.3390/toxins16070312 PMID: 39057952

Objective: To generate stable and high-affinity nanotags, via an efficient freezing method, to serve as the capture module for surface-enhanced Raman spectroscopy (SERS) and lateral flow assay (LFA) (SERS-LFA).

Summary: The detection method demonstrated good inter-batch and intra-batch reproducibility among the test strips, and the detection could be completed within 15 min, indicating the suitability of this SERS-LFA method for the on-site rapid detection of abrin and ricin toxins.

Usage: The specificity of the test strip for abrin was assessed against RCA120, AAG, RTB, RTA, Stx1, Stx2, saporin, and SEB. Proteins, such as RTA, Stx 1, Stx 2,saporin, and SEB, did not cross-react with this assay.

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Kolster M, Sonntag A, Weise C, Correa J, Fuchs H, Walther W, Fernandez-Megia E, Weng A (2024) Broadening the scope of sapofection: Cationic peptide-saponin conjugates improve gene delivery in vitro and in vivo. ACS Appl Mater Interfaces doi: 10.1021/acsami.4c05846 PMID: 38970470

Objective: Using Saponin to enhance delivery of gene therapies to cancer cells

Summary: Saponins hold promise in enhancing the endosomal escape of gene therapy vectors into cells, thereby increasing efficacy. The Saponin, SO1861, was conjugated to either a pH-sensitive peptide linker or Saporin, and internalization of the payload was measured. Saponin was shown to enhance delivery of gene therapies to cells of an aggressively growing neuroblastoma allograft model in mice.

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Branco F, Cunha J, Mendes M, Vitorino C, Sousa JJ (2024) Peptide-hitchhiking for the development of nanosystems in glioblastoma. ACS Nano 18(26):16359-16394. doi: 10.1021/acsnano.4c01790 PMID: 38861272

Objective: To review single and multiligand strategies to deliver therapeutic treatment to Glioblastoma (GBM).

Summary: The exploration of multitargeting ligands has shown great promise in GBM treatment, particularly when compared to single-targeting approaches. These ligands simultaneously use different peptides to engage a range of overexpressed receptors. These advanced strategies enhance the precision of drug delivery, facilitate BBB penetration, and enable targeting specific molecular pathways within the complex microenvironment of GBM.

Usage: ApoE-modified saporin-loaded chimeric polymersomes showed a highly efficient crossing of the BBB and accumulation in GBM.

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Kumawat C, Takahashi T, Date I, Tomita Y, Tanaka M, Arataki S, Komatsubara T, Flores AOP, Yu D, Jain M (2024) State-of-the-art and new treatment approaches for spinal cord tumors. Cancers (Basel) 16(13):2360. doi: 10.3390/cancers16132360 PMID: 39001422

Objective: To discuss innovative approaches in treating spinal cord tumors.

Summary: Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body’s own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach.

Usage: A notable study by Yan et al. involved a novel bone-targeted protein nanomedicine that combines saporin with a boronated polymer, encapsulated in an anionic poly (aspartic acid) layer. In mouse models, these nanoparticles accumulated in the bone and released saporin in response to the acidic tumor environment, effectively inactivating ribosomes and inducing cancer cell death.

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

See Also:

• Yan Y et al. Targeted and intracellular delivery of protein therapeutics by a boronated polymer for the treatment of bone tumors. Bioact Mater 7:333-340, 2021.

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)