N6L-functionalized nanoparticles for targeted and inhibited pancreatic cancer cells

• Published in: Colloids and surfaces. A, Physicochemical and engineering aspects Vol. 607; p. 125461
• Main Authors: Belbekhouche, Sabrina, Cossutta, Mélissande, Habert, Damien, Hamadi, Séna, Modjinou, Tina, Cascone, Ilaria, Courty, José
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 20.12.2020; Elsevier
• Subjects: Chemical Sciences; Gold nanoparticle; Layer-by-layer assembly; Nanocapsules; Nucleolin; Pancreatic cancer; Templating method; Templating method; Layer-by-layer assembly; Nucleolin; Pancreatic cancer; Gold nanoparticle; Nanocapsules
• ISSN: 0927-7757; 1873-4359
• DOI: 10.1016/j.colsurfa.2020.125461

[Display omitted] Pancreatic cancer is a growing cause of concern, leading to an increasing number of deaths worldwide. Most of the antitumor drugs for pancreatic cancer are given by systemic administration. However, even if this is at therapeutic doses, its tends to lead to severe side-effects because of nonspecific uptake by healthy tissues. In this context, we aim to develop an innovative drug delivery approach for the treatment of pancreatic cancer based on tailor-made nanomaterials with presenting controlled size, chemistry and stiffness. In this study, we have designed tailor-made N6L-nanomaterials, via the combination of both a templating method and a self-assembly process onto colloidal gold nanoparticles (diameters 20 nm and 60 nm) using a core template. The removal of the core leads to hollow particles, also called capsules. We judiciously functionalised the outer layer of the nanomaterial with N6L, which corresponds to a synthetic agent that is non-toxic to normal mammalian cells, targets surface nucleolin and induces tumour cell death by apoptosis. Our data demonstrated, via quartz crystal microbalance measurement, the possibility of directly using N6L in a self-assembly process through electrostatic interactions. In addition, as shown by measuring zeta potential values, we showed that electrostatic interactions between the protonated amine groups of poly (allylamine) macromolecules (+40 mV), the sulphate groups of dextran derivatives (−20 mV) and the protonated amine groups of N6L (+20 mV) are the driving attraction force during multilayer fabrication onto colloidal gold. Transmission electron microscopy was used to confirm that the gold nanoparticles were coated and the nanocapsules were formed. Finally, we successfully showed that these N6L-based nanostructures target cancer cells and inhibited, in a dose dependent manner, cell survival in pancreatic cancer model. This result clearly highlights the potential antitumor activity of the developed nanostructures.