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Common Medicines from Herbs, Minerals and Animal Sources
Published in Mehwish Iqbal, 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
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
R. G. Aswathy, D. Sakthi Kumar
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.
Hybrid Nanosystems
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Pablo Vicente Torres-Ortega, Laura Saludas, Jon Eneko Idoyaga, Carlos Rodríguez-Nogales, Elisa Garbayo, María José Blanco-Prieto
Many studies have also focused on exploring the potential of HNs formed by an inorganic core coated with functional molecules in brain cancer. Iron oxide NPs (IONPs) and quantum dots (QDs) can be found within this type of nanosystem. In most cases, these formulations led to the development of promising diagnostic tools for application in brain tumours. In this regard, Tomanek et al. determined the accumulation of a targeted contrast agent in tumour vessels using a GBM mouse model. In this case, SPIO coated with dextran and functionalised with anti-insulin-like-growth-factor binding protein 7 single-domain antibody was synthesised. For the in vivo fluorescence follow up study, a near infrared marker (Cy5.5) was also attached to the formulation, and a GBM-targeted contrast agent was obtained. The formulation was administered to U87MGdEGFRvIII tumour-bearing nude mice, leading to HN accumulation in the tumour, as demonstrated by in vivo imaging techniques and magnetic resonance imaging (MRI). These results confirmed that HNs were able to selectively bind to abnormal vessels within a glioblastoma [14]. Nevertheless, this approach needs to be further explored in order to find the optimal pulse sequence for the superparamagnetic-based contrast agent of GBM MRI at the high field. Similarly, Veiseh et al. synthesised a diagnostic nanoprobe consisting of an IONP coated with a biocompatible polymer-based layer of PEG-grafted chitosan, chlorotoxin and near infrared fluorophore (Cy5.5). The MRI capacity of the nanoprobe was tested in transgenic ND2:SmoA1 mice generated on a C57BL/6 background, showing an enhanced contrast on tumour areas of the brain due to the accumulation of the nanoprobe on damaged tissues compared to tumour-free areas of the brain. These results evidenced a high chlorotoxin tumour-targeting capacity and selectivity. Furthermore, the safe BBB-crossing ability of the nanoprobe was also studied, showing an innocuous toxicity profile [15]. Chlorotoxin-labelled magnetic nanovectors were also prepared by Kievit et al. for targeted gene delivery to glioma and for diagnostic purposes [16]. The developed nanovector consisted of an IONP core coated with a copolymer of PEG, chitosan and polyethylenimine. Green fluorescent protein (GFP) encoding DNA and chlorotoxin was attached to this nanovector for optical monitoring of the gene expression and for NP targeting, respectively. In vivo gene delivery was tested on mice bearing C6 xenograft flank tumours. MRI showed the accumulation of nanovectors in the tumour site, whereas the increase in GFP expression on the tumour cells revealed an enhanced nanovector uptake into the cancer cells due to the chlorotoxin [16]. This study offers an interesting point of view on glioma diagnosis. However, further studies should consider the use of an autograft glioma model to evaluate the therapeutic efficacy of the formulation on a clinically relevant glioma model and to prove safety regarding the BBB. The combination of this imaging tool with a chemotherapeutic agent should also be considered for the development of a theragnostic platform.
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.
Development of graphene based nanocomposites towards medical and biological applications
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Seyyed Mojtaba Mousavi, Foo Wah Low, Seyyed Alireza Hashemi, Chin Wei Lai, Younes Ghasemi, Sadaf Soroshnia, Amir Savardashtaki, Aziz Babapoor, Nelson Pynadathu Rumjit, Su Mei Goh, Nowshad Amin, Sieh Kiong Tiong
Recently, an in-vivo application of heptapeptide ATWLPPR (A7R) glioma-targeted drug delivery system based on GO was recently developed [79,80]. DOX was loaded onto chlorotoxin-conjugated GO (CTX–GO containing DOX with CTX–GO in ratio of 570 mg/g) and pertained high efficiency under non-covalent interactions [81]. Since DOX is pH a dependent state with introduced GO, the CTX–GO/DOX interceded the highest demonstration rate for glioma cells. Besides, the conjugation of chlorotoxin improved DOX glioma cells accumulation. The overall morphologies of cellular circulation and DOX, GO/DOX, and CTX–GO/DOX are illustrated in Figure 9. The cellular circulation of CTX-GO/DOX and DOX, GO/DOX, in C6 cells with the comparable concentration of DOX (0.5 mg/ml) was in incubation for 24 h. Wang et al. introduced a novel nanoparticles based on the galactosylated chitosan/GO/doxorubicin (GC–GO–DOX) drug for therapeutic cancer treatment [82]. The working drug delivery system is majorly contributed by GC and GO carriers. In this context, the drug delivery could be delivered at a maximum rate of 1.08 mg/mg (drug/polymer). The GC–GO–DOX drug remained stable under physiological conditions, whereas the drug was responsive when released at a low pH environment (tumour environment). Cells uptook the experiment on a cell propagation analysis in which the nanoparticles had a cytotoxicity rate in the sequence of HepG2 > SMMC-7721 > CS–GO–DOX. Other than the CS–GO–DOX complexity, HepG2 and SMMC-7721 exhibited higher fluorescence intensity in tumour cells.
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].