Chlorotoxin Conjugated with Saporin Reduces Viability of ML-1 Thyroid Cancer Cells In Vitro

Rizvanovic, Husref; Ad, Pinheiro; K, Kim; Thomas, Johnson

doi:10.1101/2019.12.20.885483

Cited by 2 publications

(4 citation statements)

References 28 publications

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“…Chlorotoxin inhibits the enzymatic activity of MMP-2 and therefore reduces the surface expression of MMP-2. The in vitro studies showed that CTX-SAP decreased the number of ML-1 thyroid cancer cells in a dose-dependent manner [ 37 ].…”

Section: Behavior Disease and Animal Modelsmentioning

confidence: 99%

“…This reaction has been widely studied and described and has proven itself to be an appropriate choice for a modular way of screening targeting agents. It was largely seen as an advantage to have one molecule that can be utilized both in vitro [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ] and in vivo [ 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. This modularity provided researchers the advantage of developing and planning larger-scale projects from preliminary in vitro beginnings to late-stage in vivo behavioral studies, all using the same verified reagent.…”

Section: Introduction Of Streptavidin-saporin: Trade Name—streptavidi...mentioning

confidence: 99%

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Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins

Ancheta

Shramm

Bouajram

et al. 2023

Toxins

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Streptavidin-Saporin can be considered a type of ‘secondary’ targeted toxin. The scientific community has taken advantage of this conjugate in clever and fruitful ways using many kinds of biotinylated targeting agents to send saporin into a cell selected for elimination. Saporin is a ribosome-inactivating protein that causes inhibition of protein synthesis and cell death when delivered inside a cell. Streptavidin-Saporin, mixed with biotinylated molecules to cell surface markers, results in powerful conjugates that are used both in vitro and in vivo for behavior and disease research. Streptavidin-Saporin harnesses the ‘Molecular Surgery’ capability of saporin, creating a modular arsenal of targeted toxins used in applications ranging from the screening of potential therapeutics to behavioral studies and animal models. The reagent has become a well-published and validated resource in academia and industry. The ease of use and diverse functionality of Streptavidin-Saporin continues to have a significant impact on the life science industry.

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Section: Behavior Disease and Animal Modelsmentioning

confidence: 99%

Section: Introduction Of Streptavidin-saporin: Trade Name—streptavidi...mentioning

confidence: 99%

Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins

Ancheta

Shramm

Bouajram

et al. 2023

Toxins

View full text Add to dashboard Cite

show abstract

“…The exact mechanisms by which CTX targeting occurs are not completely understood but potential primary cell surface targets have been identified over the years ( Figure 2 ). Some studies have shown that CTX is an effective blocker of small conductance epithelial chloride channels [ 118 , 119 ] and mainly binds to overexpressed cancer cell surface receptors involved in the progression of tumors such as ClC-3 (chloride channel-3) in GB cells [ 37 , 38 , 110 , 119 , 120 , 121 , 122 , 123 , 124 ] which forms a protein complex with matrix metalloprotease-2 receptor (MMP-2) [ 48 , 49 , 50 , 116 , 125 , 126 ]; annexin A2 which is present in various cell lines [ 51 , 52 ] and has since been shown to be a potential target of CTX, and more recently estrogen receptor alpha (ERα) [ 53 ] and the Neuropilin-1 (NRP-1) [ 54 , 55 ] which is a vascular endothelial growth factor receptor responsible for tumor uptake. These molecules provide alternative methods for CTX targeting tumors in cancer diagnosis and therapy.…”

Section: Chlorotoxin (Ctx): a Promising Natural Targeting Peptide For...mentioning

confidence: 99%

“…From the literature, it is proposed that ClC-3 and MMP-2 form a protein complex that is targeted by the CTX-peptide, and this action is thought to inhibit glioma cell migration and invasion through the induction of endocytosis of the MMP-2/ClC-3 protein complex [ 38 , 48 , 124 ]. Hence, CTX targeting MMP-2 has been widely investigated and proposed as one of the main molecular mechanisms for the development of CTX-based treatments for gliomas [ 48 , 49 , 50 , 53 , 112 , 114 , 115 , 116 , 125 , 148 ].…”

Section: Chlorotoxin (Ctx): a Promising Natural Targeting Peptide For...mentioning

confidence: 99%

Diagnostic and Therapeutic Approaches for Glioblastoma and Neuroblastoma Cancers Using Chlorotoxin Nanoparticles

Boltman

Meyer

Ekpo

2023

Cancers

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Glioblastoma multiforme (GB) and high-risk neuroblastoma (NB) are known to have poor therapeutic outcomes. As for most cancers, chemotherapy and radiotherapy are the current mainstay treatments for GB and NB. However, the known limitations of systemic toxicity, drug resistance, poor targeted delivery, and inability to access the blood-brain barrier (BBB), make these treatments less satisfactory. Other treatment options have been investigated in many studies in the literature, especially nutraceutical and naturopathic products, most of which have also been reported to be poorly effective against these cancer types. This necessitates the development of treatment strategies with the potential to cross the BBB and specifically target cancer cells. Compounds that target the endopeptidase, matrix metalloproteinase 2 (MMP-2), have been reported to offer therapeutic insights for GB and NB since MMP-2 is known to be over-expressed in these cancers and plays significant roles in such physiological processes as angiogenesis, metastasis, and cellular invasion. Chlorotoxin (CTX) is a promising 36-amino acid peptide isolated from the venom of the deathstalker scorpion, Leiurus quinquestriatus, demonstrating high selectivity and binding affinity to a broad-spectrum of cancers, especially GB and NB through specific molecular targets, including MMP-2. The favorable characteristics of nanoparticles (NPs) such as their small sizes, large surface area for active targeting, BBB permeability, etc. make CTX-functionalized NPs (CTX-NPs) promising diagnostic and therapeutic applications for addressing the many challenges associated with these cancers. CTX-NPs may function by improving diffusion through the BBB, enabling increased localization of chemotherapeutic and genotherapeutic drugs to diseased cells specifically, enhancing imaging modalities such as magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), optical imaging techniques, image-guided surgery, as well as improving the sensitization of radio-resistant cells to radiotherapy treatment. This review discusses the characteristics of GB and NB cancers, related treatment challenges as well as the potential of CTX and its functionalized NP formulations as targeting systems for diagnostic, therapeutic, and theranostic purposes. It also provides insights into the potential mechanisms through which CTX crosses the BBB to bind cancer cells and provides suggestions for the development and application of novel CTX-based formulations for the diagnosis and treatment of GB and NB in the future.

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Chlorotoxin Conjugated with Saporin Reduces Viability of ML-1 Thyroid Cancer Cells In Vitro

Abstract: All authors contributed equally to this work 17 Running title: CTX-SAP decreases ML-1 cell viability 18 Abstract 20 Background 21 Although differentiated thyroid cancer has good prognosis, radioactive iodine (RAI) 22

Cited by 2 publications

References 28 publications

Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins

Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins

Diagnostic and Therapeutic Approaches for Glioblastoma and Neuroblastoma Cancers Using Chlorotoxin Nanoparticles

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