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Photoacoustic Imaging and Therapy Utilizing Molecular Specific Plasmonic Nanoparticles
Published in Lihong V. Wang, Photoacoustic Imaging and Spectroscopy, 2017
Stanislav Emelianov, Mallidi Srivalleesha, Timothy Larson, Konstantin Sokolov
EGFR is overexpressed in many types of tumors. The clustering of anti-EGFR conjugated gold nanoparticles leads to plasmon resonance coupling between nanoparticles and a red shift in the plasmon resonance frequency of the gold nanoparticle assembly [4,5,10]. Based on these concepts, we demonstrated that highly sensitive and selective detection of cancer could be achieved using molecular targeted gold nanosensors and combined photoacoustic and ultrasound imaging [2]. We have also demonstrated that molecular specific plasmonic nanoparticles could assist pulsed laser phototherapy. Indeed, the combined photoacoustic imaging and phototherapy approach could potentially use the same light source, where low laser irradiation levels can be used to generate photoacoustic transients and detect cancerous tissue, followed by high doses of nonionizing light irradiation to perform phototherapy. In addition, ultrasound imaging can be used to accurately plan and guide the therapy and to monitor the outcome [21]. Further studies are required to evaluate this molecular specific imaging technique in vivo and its potential in combination with phototherapy.
Neutron Capture Therapy of Cancer: Nanoparticles and High Molecular Weight Boron Delivery Agents
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Gong Wu, Rolf F. Barth, Weilian Yang, Robert J. Lee, Werner Tjarks, Marina V. Backer, Joseph M. Backer
Due to its increased expression in a variety of tumors, including high-grade gliomas, and its low or undetectable expression in normal brain, EGFR is an attractive target for cancer therapy.68–70 As described above, targeting of EGFR has been carried out using either mAbs or alternatively, as described in this section, EGF, which is a single-chain, 53-mer heat and acid stable polypeptide. It binds to a transmembrane glycoprotein with tyrosine kinase activity, which triggers dimerization and internalization.71,72 Because the EGF boron bioconjugates have a much smaller MW than mAb conjugates, they should be capable of more rapid and effective tumor targeting than has been observed with mAbs.67,73
Drug Targeting: Principles and Applications
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Drug Delivery Approaches and Nanosystems, 2017
Ruslan G. Tuguntaev, Ahmed Shaker Eltahan, Satyajeet S. Salvi, Xing-Jie Liang
The EGFR is a member of tyrosine kinase receptors family. Its activation promotes key processes involved in tumor growth and progression, such as proliferation, angiogenesis invasion and metastasis (Lurje et al., 2009). EGFR is overexpressed in many solid tumors such as non-small cell lung cancer, breast, squamous cell carcinoma of the head and neck, ovarian, kidney, prostate, and pancreatic cancer. Usually EGFR expression characterizes a more advanced disease stage and its presence corresponds directly to the metastatic capabilities in various types of cancer (Byrne et al., 2008). Expression of EGFR on tumor cells is much higher than normal cells making EGFR appropriate candidate for selective drug delivery.
Theoretical validation of some third-generation epidermal growth factor receptor (EGFR) Inhibitors as non-small cell lung cancer (NSCLC) drugs
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Muhammad Tukur Ibrahim, Adamu Uzairu
Epidermal growth factor receptor (EGFR) was discovered in the University of Vanderbilt (USA) by a scientist named Stanley Cohen in 1956 [5]. EGFR is a member of the receptor tyrosine kinase (RTK) and belongs to the ErbB family of proteins that regulate essential cellular roles, such as cell division, growth, differentiation, metabolism, adhesion, motility and death [6]. It was recognized as the principal target for the treatment of NSCLC [7].
Mutation patterns of epidermal growth factor receptor gene in non-small cell lung cancer among Egyptian patients
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Wafaa H. Elmetnawy, Mona Qenawi, Salwa Sabet, Heba Bassiony
The discovery of oncogenic driver mutations in NSCLC patients over the past 20 years has led to new molecular targeted therapies that have dramatically improved treatment efficacy and quality of life [16]. Over-expression of EGFR is associated with angiogenesis and poor prognosis in 50% – 80% NSCLC patients, and that makes it a prime candidate for targeted therapy [17]. EGFR is a transmembrane glycoprotein with cytoplasmic tyrosine kinase activity consisting of an extracellular ligand-binding domain, a transmembrane domain, an intracellular tyrosine kinase (TK) domain and a regulatory region [18]. After ligand binding, specific tyrosine residues of the intracellular domain are autophosphorylated, leading to the initiation of intracellular signaling cascades, including the Ras/Raf/MAPK, JAK/ STAT and PI3K-Akt pathways, this results in a number of consequences including cell proliferation, cell differentiation, angiogenesis, metastasis and anti-apoptosis [19]. Mutations in the EGFR enhance cell proliferation through increasing downstream signaling. The molecular characterization of advanced NSCLC adenocarcinoma in recent years had participated in identifying several driver events, including EGFR constitutive activation [20]. EGFR gene is frequently amplified, and/or mutated in lung adenocarcinoma. In NSCLC cases; EGFR is highly expressed and coding for tyrosine kinase receptor [21]. EGFR mutation analysis is considered as an essential biomarker in the controlling of advanced lung adenocarcinoma, assessment of responsiveness to tyrosine kinase inhibitors (TKIs) [22–24], for prolonged progression free survival (PFS) and overall survival (OS) of EGFR positive NSCLC patients [25]. Therefore, it is essential to examine the basic status of EGFR mutations at diagnosis using the most trustworthy methods [23]. EGFR mutations are frequently found in adenocarcinoma, with Asians having higher rates (38.8%–64.0%) than Caucasians (4.9%–17.4%). Exon 19 deletions and exon 21 leucine to arginine substitutions (L858R) are the most frequent EGFR mutations, accounting for about 90% of all EGFR mutations. Furthermore, exons 18 and 20 also have mutations that are less prevalent [26].
Improved anti-cancer effect of epidermal growth factor-gold nanoparticle conjugates by protein orientation through site-specific mutagenesis
Published in Science and Technology of Advanced Materials, 2021
Nowadays, cancer is still one of the leading causes of death in the world [1]. Treatment of cancer by chemotherapy, surgery, and radiation therapy has been proven to be effective in treating many cells. However, most of them are accompanied with harmful side effects to normal cells, therefore the development of new therapeutic methods is urgently needed [2–4]. The nanomedicine, including nanoparticle-based and two-dimensional (2D) nanoarchitecture-based vehicles, which carrying chemical drugs or protein/peptide drugs are promising to be the new generation medicines due to the improved capacity of the drug-loading, efficacy of cell uptake, and biocompatibility [5–8]. However, the specify of them still needs to be enhanced to selectively kill tumor cells and reduce cytotoxic effects to the normal cells. Recently, the epidermal growth factor receptor (EGFR)-targeted cancer therapeutics has been developed due to the overexpression of EGFR in many tumors [9]. The EGFR is the membrane receptor and plays an important role in cell growth and proliferation [10]. Abnormally activated EGFR by receptor overexpression, mutation, and ligand-independent activation can result in the development of cancer [11]. Therefore, specific EGFR inhibition is one of the promising methods for cancer therapy. There are two major approaches of EGFR inhibition with different mechanism by using monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). The mAbs (cetuximab, panitumumab) against EGFR are designed specifically to recognize extracellular domain of EGFR to compete with endogenous ligands of EGFR, leading to the inhibition of activation of the EGFR tyrosine kinase induced by the ligand [11–14]. The TKIs such as gefitinib, erlotinib, and canertinib, are small molecules which bind to the intracellular catalytic domain of EGFR tyrosine kinase to compete with adenosine-5ʹ-triphosphate (ATP), inhibiting autophosphorylation and activation of downstream signaling [11,12,15]. Both strategies of inhibition of EGFR have been approved for clinical use and have effective anti-cancer activity. In spite of the effective treatment, it is still difficult to completely cure patients due to the developed resistance of tumor to the EGFR inhibitors. Therefore, the development of new anti-EGFR drugs based on different approaches are expected. Recently, it has been identified that the conjugation of epidermal growth factor (EGF) to gold nanoparticles (GNPs) can gain an enhanced apoptotic efficiency in cancer cells [16,17]. Our group has identified that the emergent unique apoptosis activities of the EGF-GNP conjugates were attributed to the confinements of EGFR within lipid rafts and selective activation of extracellular signal-regulated kinase (ERK) [18]. The EGF conjugates is promising due to the alternative apoptosis pathway of EGFR to overcome the limitation of resistance of inhibitors, and it allows precise delivery of the therapeutics to the intended cell targets which overexpressed EGFR.