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The physiological and pathological mechanisms of LIN2, LIN7, LIN10 and their tripartite complex
Shang Y, Gan X, Dang Y, Liu J, Liu P (2025) The physiological and pathological mechanisms of LIN2, LIN7, LIN10 and their tripartite complex. J Cell Mol Med 29(15):e70794. doi: 10.1111/jcmm.70794 PMID: 40801824
Objective: To furnish a robust theoretical foundation for the prospective utilization of polarity proteins and their complex as cancer markers and therapeutic targets.
Summary: Authors have found that LIN2, LIN7, and LIN10, as well as their complexes, play important roles in the establishment and maintenance of apical-basal polarity. They are also involved in two physiological processes: synaptic transmission and receptor localization. Additionally, LIN2, LIN7, and LIN10 are linked to the pathological processes of type 2 diabetes mellitus and cardiovascular diseases. Meanwhile, they regulate the proliferation, apoptosis, and metastasis of cancer cells through various pathways.
Usage: The PDZ domain of LIN2 can target binding to CD98, a negative prognostic marker for human glioblastoma cells. Constructing a chimera of the PDZ domain of LIN2 with the ribosome-inactivating protein Saporin (PR-01) and enhancing the activity of this chimera as the number of PDZ domains increases can effectively increase cytotoxicity and apoptosis in human glioblastoma cells, GL15 and U87.
Related Products: Saporin (Cat. #PR-01)
Nanoparticle-based delivery strategies for combating drug resistance in cancer therapeutics
Park S, Lu GL, Zheng YC, Davison EK, Li Y (2025) Nanoparticle-based delivery strategies for combating drug resistance in cancer therapeutics. Cancers (Basel) 17(16):2628. doi: 10.3390/cancers17162628 PMID: 40867257
Objective: To explore how nanoparticle-based drug delivery systems can address the challenge of resistance to chemotherapy and targeted therapy by improving drug accumulation in tumors, enhancing targeting specificity, and enabling controlled or stimulus-responsive drug release.
Summary: Nanoparticle-based drug delivery strategies offer a promising and multifaceted approach to overcoming multidrug resistance in cancer therapy. Nanocarriers can address many limitations and challenges associated with conventional chemotherapy by enhancing the intracellular drug accumulation at tumor sites, bypassing efflux transporters, facilitating targeted delivery, and enabling in vivo gene modulation.
Usage: Lipid-saporin nanoparticles were utilized to bypass efflux transporters via the co-delivery of anticancer drugs with ABC transporters, leading to an increase in intracellular drug concentrations and the re-sensitization of drug-resistant cancer cells to chemotherapy.
Related Products: Saporin (Cat. #PR-01)
Targeted delivery of cytotoxic proteins via lipid-based nanoparticles to primary Langerhans cells
Rahhal N, Rentzsch M, Seiser S, Freystätter C, Elbe-Bürger A, Rademacher C (2025) Targeted delivery of cytotoxic proteins via lipid-based nanoparticles to primary Langerhans cells. Nanoscale doi: 10.1039/d4nr03638g PMID: 39775685
Summary: Saporin was used as a model protein to showcase the potential of delivering intact proteins to Langerhans cells. Authors observed specific killing of cells expressing langerin in vitro, and in primary Langerhans cells isolated from mouse and human skin ex vivo with minimal off target effects.
Related Products: Saporin (Cat. #PR-01)
Phase-separating peptide coacervates with programmable material properties for universal intracellular delivery of macromolecules
Sun Y, Wu X, Li J, Radiom M, Mezzenga R, Verma CS, Yu J, Miserez A (2024) Phase-separating peptide coacervates with programmable material properties for universal intracellular delivery of macromolecules. Nat Commun 15(1):10094. doi: 10.1038/s41467-024-54463-z PMID: 39572548
Objective: To systematically manipulate the sequence of Phase-separating peptides (PSPs) to unravel the relationships between their molecular structure, the physical properties of the resulting coacervate microdroplets (CMs), and their delivery efficacy.
Summary: A few amino acid alterations are sufficient to modulate the viscoelastic properties of CMs towards either a gel-like or a liquid-like state as well as their binding interaction with cellular membranes, collectively enabling to tune the kinetics of intracellular cargo release. The authors also demonstrated that the optimized PSPs CMs display excellent transfection efficiency in hard-to-transfect cells such as primary fibroblasts and immune cells.
Usage: The cytotoxicity of the saporin-loaded (at various concentrations) or pristine CMs were evaluated using the Cell Counting Kit-8 (CCK-8).
Related Products: Saporin (Cat. #PR-01)
Progressive cancer targeting by programmable aptamer-tethered nanostructures
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)
Unveiling the dynamic interplay between cancer stem cells and the tumor microenvironment in melanoma: Implications for novel therapeutic strategies
Limonta P, Chiaramonte R, Casati L (2024) Unveiling the dynamic interplay between cancer stem cells and the tumor microenvironment in melanoma: Implications for novel therapeutic strategies. Cancers (Basel) 16(16):2861. doi: 10.3390/cancers16162861 PMID: 39199632
Objective: To review the bidirectional communication between melanoma cancer stem cells (CSCs) and the tumor microenvironment, highlighting its role in drug resistance and tumor relapse.
Summary: Melanoma CSCs evade immune surveillance and recruit immune cells with immunosuppressive and tumor-promoting properties, establishing a supportive microenvironment. They also transfer stemness and aggressive traits to neighboring non-CSCs, driving tumor progression and metastasis. Targeting these interactions may offer novel therapeutic strategies for combating melanoma.
Usage: This review publication highlights the usage of Anti-CD271-SAP and CD133-SAP in previous publications.
Related Products: ME20.4-SAP (Cat. #IT-15), Anti-CD133-SAP (Cat. #IT-82), Saporin (Cat. #PR-01)
See Also:
- Ngo M et al. Antibody therapy targeting CD47 and CD271 effectively suppresses melanoma metastasis in patient-derived xenografts. Cell Rep 16:1701-1716, 2016.
- Bostad M et al. Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization – A minimally invasive cancer stem cell-targeting strategy. J Control Release 206:37-48, 2015.
A bioinspired pseudopeptide-based intracellular delivery platform enhances the cytotoxicity of a ribosome-inactivating protein through multiple death pathways
Morrison G, Henry N, Kopytynski M, Chen R (2024) A bioinspired pseudopeptide-based intracellular delivery platform enhances the cytotoxicity of a ribosome-inactivating protein through multiple death pathways. Biomater Sci 12(19):5010-5022. doi: 10.1039/d4bm00600c PMID: 39177215
Objective: To overcome Saporin’s poor plasma membrane permeability.
Summary: To overcome this barrier, authors used a bioinspired intracellular delivery platform based on the pH-responsive pseudo peptide, poly (L-lysine isophthalamide) grafted with L-phenylalanine at a stoichiometric molar percentage of 50% (PP50). PP50 was co-incubated with saporin (PP50/saporin) in a mildly acidic pH environment to aid intracellular delivery and increase saporin’s therapeutic potential. It was shown that PP50 is a potential intracellular delivery platform for the internalization of protein therapeutic.
Usage: PP50/saporin formulations were prepared with D-PBS solutions at pH 6.5 containing PP50 at a specific concentration of 0.025, 0.1, 0.2, 0.5 or 5 mg mL−1 and Saporin (PR-01) at varying concentrations.
Related Products: Saporin (Cat. #PR-01)
Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases
O’Sullivan JA, Youngblood BA, Schleimer RP, Bochner BS (2024) Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases. Semin Immunol 69:101799. doi: 10.1016/j.smim.2023.101799 PMID: 37413923
Objective: To review a subset of Siglecs and their various endogenous or synthetic sialoside ligands that regulate eosinophil and mast cell function and survival.
Summary: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are vertebrate glycan-binding cell-surface proteins. Many Siglecs mediate cellular inhibitory activity and are of interest as part of a strategy to therapeutically lessen unwanted cellular responses. Human eosinophils and mast cells express overlapping but distinct patterns of Siglecs, and certain Siglecs have become the focus of novel therapies for allergic and other eosinophil and mast cell-related diseases.
Usage: Saporin in conjunction with CD22 glycomimetic ligand BPCNeuAc leads to cells death induction in a ligand-dependent manner on B-lymphoma cells (Collins et al.). Incubation with anti-Siglec-8 monoclonal antibody conjugated to saporin led to the death of malignant mast cells and eosinophils (O’Sullivan et al.)
Related Products: Saporin (Cat. #PR-01)
See Also:
- Collins BE, Blixt O, Han S, Duong B, Li H, Nathan JK, Bovin N, Paulson JC (2006) High-affinity ligand probes of CD22 overcome the threshold set by cis ligands to allow for binding, endocytosis, and killing of B cells. J Immunol 177(5):2994-3003. doi: 10.4049/jimmunol.177.5.2994 PMID: 16920935
- O’Sullivan J et al. Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells. J Allergy Clin Immunol 141:1774-1785.e1777, 2018.
T cell death-associated gene 8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain
Dai SP, Yang CC, Chin Y, Sun WH (2024) T cell death-associated gene 8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain. iScience 27(10):110955. doi: 10.1016/j.isci.2024.110955 PMID: 39381739
Objective: To elucidate how T cell death-associated gene 8 (TDAG8)-mediated signaling modulates neuron activities in a mouse model of chronic constriction injury-induced neuropathic pain.
Summary: TDAG8 participated alone in mechanical allodynia induced by constriction injury. TDAG8-Nav1.8 signaling in small-diameter isolectin B4-positive [IB4(+)] neurons initiate mechanical allodynia; it also modulated substance P release from IB4(-) neurons to facilitate the development of early mechanical allodynia. TDAG8-mediated signaling increased medium-to large-diameter IB4(-) neuron activity to maintain late mechanical allodynia; it also modulated substance P release in soma to reduce satellite glial number and Nav1.7 expression, thus attenuating chronic mechanical allodynia.
Usage: Mice were intrathecally injected with IB4-saporin (IB4-SAP, 0.06 mg/mL) or Saporin (0.06 mg/mL)
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Rational engineering of cytosolic delivery systems for protein therapeutics
Lv J, Liu X, Yin L, Cheng Y (2024) Rational engineering of cytosolic delivery systems for protein therapeutics. Acc Mater Res doi: 10.1021/accountsmr.4c00149
Objective: To summarize recent advances in the rational design of cytosolic protein delivery systems.
Summary: Saporin, a cell membrane-impermeable toxin, kills cancer cells by inhibiting protein synthesis. To fully utilize the therapeutic potential of saporin, the authors developed a series of polymeric carriers to deliver saporin into tumor cells.
Usage: Polymeric carriers were used to deliver saporin into tumor cells
Related Products: Saporin (Cat. #PR-01)
