Novel PAMAM-PEG-Peptide Conjugates for siRNA Delivery Targeted to the Transferrin and Epidermal Growth Factor Receptors

• Published in: Journal of personalized medicine Vol. 8; no. 1; p. 4
• Main Authors: Urbiola, Koldo, Blanco-Fernández, Laura, Ogris, Manfred, Rödl, Wolfgang, Wagner, Ernst, Tros de Ilarduya, Conchita
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.01.2018; MDPI
• Subjects: Epidermal growth factor; Epidermal growth factor receptors; Gene silencing; Growth factor receptors; Nanoparticles; Precision medicine; siRNA; Transferrins; Tumor cells; Zeta potential; polyethylenglycol; gene silencing; nanotechnology; gene therapy; cancer; cationic polymers
• ISSN: 2075-4426; 2075-4426
• DOI: 10.3390/jpm8010004

The transferrin (TfR) and epidermal growth factor receptors (EGFR) are known to be overexpressed on the surface of a wide variety of tumor cells. Therefore, the peptides B6 (TfR specific) and GE11 (targeted to the EGFR) were linked to the PAMAM (polyamidoamine) structure via a polyethylenglycol (PEG) 2 kDa chain with the aim of improving the silencing capacity of the PAMAM-based dendriplexes. The complexes showed an excellent binding capacity to the siRNA with a maximal condensation at nitrogen/phosphate (N/P) 2. The nanoparticles formed exhibited hydrodynamic diameters below 200 nm. The zeta potential was always positive, despite the complexes containing the PEG chain in the structure showing a drop of the values due to the shielding effect. The gene silencing capacity was assayed in HeLa and LS174T cells stably transfected with the eGFPLuc cassette. The dendriplexes containing a specific anti luciferase siRNA, assayed at different N/P ratios, were able to mediate a mean decrease of the luciferase expression values of 14% for HeLa and 20% in LS174T cells, compared to an unspecific siRNA-control. ( < 0.05). In all the conditions assayed, dendriplexes resulted to be non-toxic and viability was always above 75%.