Intraoperative Infrared Optical Imaging in Neurosurgery
Yu Chen, Babak Kateb in Neurophotonics and Brain Mapping, 2017
Tumor paint is a new and radical brain tumor imaging agent that was initially discovered by pediatric oncologist James Olson and his team at the Fred Hutchinson Cancer Research Center and Seattle Children’s Hospital Research Institute. Tumor paint comprises a molecule that consists of a NIR fluorophore that is conjugated with chlorotoxin (CTX), a peptide found in the venom of the Israeli deathstalker scorpion (Leiurus quinquestriatus). The CTX portion preferentially binds to glioma cells (Soroceanu et al. 1998) and other tumors of neuroectodermal origin (Lyons et al. 2002) in contrast to normal brain cells. There have been no reports of toxicity in the use of CTX during in vivo studies (Stroud et al. 2011).
Common Medicines from Herbs, Minerals and Animal Sources
Mehwish Iqbal in Complementary and Alternative Medicinal Approaches for Enhancing Immunity, 2023
Despite the life-threatening and hazardous outcomes of scorpion envenoming, the healing properties of scorpion venoms and body parts in traditional medicine have been recognised by humans for millennia (Petricevich, 2010). It is extensively documented in the texts that scorpion venom is enriched with bioactive constituents, and as such, the toxin of scorpions is of great interest to the medicine-making industries (Kerkis et al., 2017). Despite the fact that significant research efforts are kept going, and the likelihood for scorpion-originated medicinal peptides is extremely promising, the only toxin that has been chosen for clinical studies from the venom of the scorpion is chlorotoxin (Ahmadi et al., 2020).
Magnetic Nanoparticles for Cancer Diagnosis
D. Sakthi Kumar, Aswathy Ravindran Girija in Bionanotechnology in Cancer, 2023
Although the application of antibody for tumor targeting is considered to be appropriate, the antibody NPs conjugate suffers from several disadvantages, such as large hydrodynamic size and poor diffusion and uptake by RES. Therefore, small targeting moieties are gaining more attention. Arginine-glycine-aspartic acid (RGD) [70–73] peptides are often coupled with IO NPs for the detection of various cancers, including breast cancer, squamous cell carcinomas, and malignant melanomas. Owing to the multivalent binding property, binding efficacy of IO particles to the RGD peptide can be improved. Thus, more numbers of RGD peptides have been attached to the IO particles, due to their very small size and multivalent binding property [74]. Another functional peptide employed was Chlorotoxin (36 amino acid peptide), concurrently used for both molecular imaging by MRI and tumor therapeutics [75]. Adhesion molecule vascular cell adhesion protein 1 (VCAM-1) was recognized as a target for macrophage and endothelial cells that may lead to atherosclerosis. VCAM-1 targeted peptide was conjugated with MNPs and MRI contrast enhancement of early lesions in juvenile mice and resected human carotid artery plaques was observed [76]. Studies of in vitro cellular targeting experiments suggest that Fe3O4-folic acid (FA) nanoconjugate binds specifically to tumor cells [66]. Tumor detection studies with SPIO-PEG-FA as MRI contrast agent demonstrated signal intensity difference in positive in human nasopharyngeal epidermal carcinoma cells (KB cells) tumors (around 20–25%), which was considerably less than the negative HT-1080 cell tumor from pre-contrast to post-contrast image of the tumor in in vivo MR imaging.
Advances in venom peptide drug discovery: where are we at and where are we heading?
Published in Expert Opinion on Drug Discovery, 2021
Taylor B. Smallwood, Richard J. Clark
Today, there are numerous venom-derived peptides in clinical and preclinical development (Table 2). Chlorotoxin is a 36-amino acid neurotoxin peptide isolated from the venom of Leirurus quinquestriatus, the death stalker scorpion [25]. The peptide was first discovered in 1993 after previous studies showed that the L. quinquestriatus scorpion crude venom extract inhibited reconstituted small-conductance chloride channels isolated from rat epithelia and embryonic rat brain [26]. Interestingly, unlike many peptides, chlorotoxin is able to cross the bblood–brain barrier (BBB) and penetrate deep internal tissues or firm tumors [27]. Due to the peptide preferentially binding to glioma cells, the synthetic analogue TM-601, has undergone clinical trials for its use to treat malignant glioma (NCT00379132, NCT00040573). Tozuleristide (BLZ-100) is a tumor targeting agent ccomprisedchlorotoxin linked to a fluorescent dye, indocyanine green. Using near-infrared fluorescence imaging system, a clear distinction can be made between healthy tissue and tumor cells, facilitating the surgical removal of tumor tissue. A clinical trial (NCT03579602) for tozuleristide is currently undergoing patient recruitment for the use of the chlorotoxin analogue as an investigational imaging agent in pediatric subjects with central nervous system (CNS) tumors undergoing surgery.
Recent CPP-based applications in medicine
Published in Expert Opinion on Drug Delivery, 2019
Chlorotoxin is an interesting example of natural peptides, which has been isolated from the venom of the deathstalker scorpion (Leiurus quinquestriatus) and which has specific anticancer properties. The peptide is 36-amino acid long, but due to its α-helix and three-stranded antiparallel β-sheets, very compact. Its cancer binding and mechanism of action has not been fully elucidated, but it seems that binding to alpha-v integrins, MMP2, or chloride channels is involved in its inhibiting activity to glioma cell migration and invasion [27]. It has shown excellent penetration deep into glioma [27], which has been utilized by conjugating it with the fluorophore Cy5.5 and it is being marketed as cancer diagnostic ‘Tumor Paint’ for the fluorescence-guided surgery. The advantage over the traditional clinically used 5ALA is that it does not need topical administration. Instead, Chlorotoxin is administered intravenously and it offers longer circulation within the body prior to surgery. Currently, Chlorotoxin and its various analogs are in several stages of clinical trials for brain and skin cancers. Its derivatives have demonstrated glioma targeting in a number of studies, including radiolabeled, fluorescent, and nanoparticle-based derivatives [27,28].
Targeting central nervous system pathologies with nanomedicines
Published in Journal of Drug Targeting, 2019
Shoshy Mizrahy, Anna Gutkin, Paolo Decuzzi, Dan Peer
Chlorotoxin (CTX) is a 36 residue peptide derived from the venom of the Israeli scorpion Leiurus quinquestriatus [127]. This peptide has been used in multiple CNS delivery systems and even matured to clinical trials due to its ability to preferentially bind to brain tumour cells and high stability derived from its 8 cysteines that form 4 disulphide bonds [127–129]. The preferential binding of malignant tissue may be related to CTX’s specific interaction with metalloprotease-2 (MMP-2), which is overexpressed in brain tumours. Additional advantages for CTX from a drug delivery standpoint are its lack of toxicity and immunogenicity and demonstrated the ability to enter the brain upon IV administration, suggesting that it might be able to cross the BBB directly [127]. CTX has also been shown to possess antiangiogenic activity, an additional advantage for cancer therapy [130].
Related Knowledge Centers
- Chloride Channel
- Cysteine
- Disulfide
- Peptide
- Scorpion Toxin
- Venom
- Amino Acid
- Glioma
- Superfamily Database
- Sequence Homology