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Cellular imaging and time-domain FLIM studies of meso-tetraphenylporphine disulfonate as a photosensitising agent in 2D and 3D models
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)
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- 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
Targeted therapy for multiple myeloma: an overview on CD138-based strategies
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)
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Increased systemic levels of centrally acting b-type natriuretic peptide are associated with chronic itch of different types
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)
Polymersomes for therapeutic protein and peptide delivery: Towards better loading properties
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)
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Therapeutic peptides and proteins: Stabilization challenges and biomedical applications by means of nanodelivery systems
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)
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Engineering small protein based inhibitors and biodegraders for cytosolic delivery and targeting of the undruggable proteome
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).
Women’s special issue series: Biomedicines
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.
Investigating the cytosolic delivery of proteins by lipid nanoparticles using the chloroalkane penetration assay
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)
Chemical and biological characterization of vaccine adjuvant QS-21 produced via plant cell culture
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)
Endosialin in cancer: Expression patterns, mechanistic insights, and therapeutic approaches
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)
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