Cytotoxic chemotherapy is the standard of care for many types of cancer despite the frequently observed severe side effects. The targeted delivery of chemotherapeutics has great potential to reduce these effects by increasing drug concentrations within the target tissue, thereby reducing their required dose [1]. Compared to larger nanoparticles, Midatech’s ultrasmall gold nanoparticles are less likely to form a protein corona due to their very small size and carbohydrate based ligand shell [2], which makes them especially interesting for active targeting strategies. Furthermore, their highly flexible organic ligand shell allows covalent attachment of functional molecules using several biocompatible coupling techniques.
In this work we demonstrate the synthesis and analysis of a nanoparticle construct able to target cell surface α6 integrins. A laminin α1-derived synthetic peptide (SIKVAV) was covalently attached to carboxylated ultrasmall gold nanoparticles using EDC/NHS coupling chemistry (Figure 1). The resulting particles were analysed using dynamic light scattering (DLS) and high performance liquid chromatography (HPLC) amongst others. Assays were developed to measure the binding and uptake of the nanoparticle construct into cells by following the gold concentration. Using these assays, binding and an increased (roughly twofold compared to the base particle) uptake into HEPG2 cells, which overexpress the integrin receptor, was observed. Specificity of the binding was demonstrated by outcompeting the binding with free peptide.
In conclusion, Midatech’s SIKVAV-functionalized gold nanoparticles preferentially bind to integrin receptor expressing cells and are therefore interesting candidates for treating tumors that overexpress the integrin receptor, such as glioblastoma [3] or hepatocellular carcinoma [4].
References
[1] S. M. Sagnella, J. A. McCarroll, M. Kavallaris, Nanomedicine 2014, 10, 1131.
[2] K. Zarschler, L. Rocks, N. Licciardello, L. Boselli, E. Polo, K. P. Garcia, L. De Cola, H. Stephan, K. A. Dawson, Nanomedicine 2016, 12 (6), 1663-1701.
[3] J. Lathia, J. Gallagher, J. M. Heddleston, J. Wang, CE. Eyler, J. Macswords, Q. Wu, A. Vasanji, R. E. McLendon, A. B. Hjelmeland, J.N. Rich, Cell Stem Cell. 2010, 6 (5), 421-32.
[4] Y. Wu, X. Qiao, S. Qiao, L. Yu, Expert Opinion on Therapeutic Targets 2011, 15(4), 421-437.
