Modulation of EGFR Activity by Molecularly Imprinted Polymer Nanoparticles Targeting Intracellular Epitopes
Piletsky S.S. Baidyuk E. Piletska E.V. Lezina L. Shevchenko K. Jones D.J.L. Cao T.H. Singh R. Spivey A.C. Aboagye E.O. Piletsky S.A. Barlev N.A.
8 November 2023American Chemical Society
Nano Letters
2023#23Issue 219677 - 9682 pp.
In recent years, molecularly imprinted polymer nanoparticles (nanoMIPs) have proven to be an attractive alternative to antibodies in diagnostic and therapeutic applications. However, several key questions remain: how suitable are intracellular epitopes as targets for nanoMIP binding? And to what extent can protein function be modulated via targeting specific epitopes? To investigate this, three extracellular and three intracellular epitopes of epidermal growth factor receptor (EGFR) were used as templates for the synthesis of nanoMIPs which were then used to treat cancer cells with different expression levels of EGFR. It was observed that nanoMIPs imprinted with epitopes from the intracellular kinase domain and the extracellular ligand binding domain of EGFR caused cells to form large foci of EGFR sequestered away from the cell surface, caused a reduction in autophosphorylation, and demonstrated effects on cell viability. Collectively, this suggests that intracellular domain-targeting nanoMIPs can be a potential new tool for cancer therapy.
cancer , epidermal growth factor receptor , epitopes , molecularly imprinted polymers , nanoparticles
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Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City Campus, London, W12 0BZ, United Kingdom
L.A. Orbeli Institute of Physiology NAS, Yerevan, 0028, Armenia
School of Chemistry, University of Leicester, Leicester, LE1 7RH, United Kingdom
Department of Cancer Studies, University of Leicester, Leicester, LE1 7RH, United Kingdom
Institute of Cytology, Saint-Petersburg, 197101, Russian Federation
Leicester Cancer Research Centre, University of Leicester, Leicester Royal Infirmary, Leicester, LE1 7RH, United Kingdom
Department of Cardiovascular Sciences, University of Leicester, Leicester, LE1 7RH, United Kingdom
National Institute for Health Research, Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE1 7RH, United Kingdom
Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London, SW7 2BX, United Kingdom
Nazarbayev University School of Medicine, 53 Kabanbay Batyr Ave, Nur-Sultan, 010000, Kazakhstan
Sechenov First Medical University, Moscow, 119992, Russian Federation
Department of Chemistry
L.A. Orbeli Institute of Physiology NAS
School of Chemistry
Department of Cancer Studies
Institute of Cytology
Leicester Cancer Research Centre
Department of Cardiovascular Sciences
National Institute for Health Research
Department of Surgery and Cancer
Nazarbayev University School of Medicine
Sechenov First Medical University
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