title: Receptor-Mediated Enhanced Cellular Delivery of Nanoparticles Using Recombinant Receptor-Binding Domain of Diphtheria Toxin.
abstract: Antibodies and peptides are often used to home nanoparticles (NPs) to specific cells. Here in this work, we have used recombinant receptor-binding domain of diphtheria toxin (RDT) as a homing molecule for NPs. Diphtheria toxin binds to heparin binding EGF-like growth factor (HB-EGF) through its receptor-binding domain. HB-EGF is often overexpressed as cell surface molecule in various types of cancer. We have prepared monodispersed, spherical PLGA NPs and coated these NPs with RDT. These NPs are characterized by FESEM and FT-IR spectroscopy. Using flow cytometry and fluorescence spectroscopy, we show that coating with RDT increases cellular uptake of PLGA NPs. We further show that RDT-coated nanoparticles are internalized through clathrin-dependent receptor-mediated endocytosis that can be reduced by specific inhibitor. These RDT-coated nanoparticles (RDT-NP) were further used for preferential delivery of Irinotecan, a chemotherapeutic agent, to cells overexpressing HB-EGF. We show that receptor-mediated enhanced uptake of RDT-NPs increases the potency of irinotecan in these cells.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati , Guwahati 781039, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Agarwal
authors.affiliation: Centre for Nanotechnology, Indian Institute of Technology Guwahati , Guwahati 781039, India.
authors.forename: Amaresh Kumar
authors.initials: AK
authors.lastname: Sahoo
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati , Guwahati 781039, India.|Centre for Nanotechnology, Indian Institute of Technology Guwahati , Guwahati 781039, India.
authors.forename: Biplab
authors.initials: B
authors.lastname: Bose
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D004167:Diphtheria Toxin / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D004815:Epidermal Growth Factor / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor / Q000378:metabolism; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D000067996:RAW 264.7 Cells; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002966:Clathrin; D004167:Diphtheria Toxin; D066257:Heparin-binding EGF-like Growth Factor; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor
keywords: HB-EGF; diphtheria toxin; endocytosis; nanoparticles; targeted delivery