Citation:

Epidermal growth factor alters silica nanoparticle uptake and improves gold-nanoparticle-mediated gene silencing in A549 cells, Susnik, Eva, Bazzoni Amelie, Taladriz-Blanco Patricia, Balog Sandor, Moreno-Echeverri {Aura Maria}, Glaubitz Christina, {Brito Oliveira} Beatriz, Ferreira Daniela, {Viana Baptista} Pedro, Petri-Fink Alke, and Rothen-Rutishauser Barbara , Frontiers in Nanotechnology, jul, Volume 5, (2023)

Abstract:

Introduction: Delivery of therapeutic nanoparticles (NPs) to cancer cells represents a promising approach for biomedical applications. A key challenge for nanotechnology translation from the bench to the bedside is the low amount of administered NPs dose that effectively enters target cells. To improve NPs delivery, several studies proposed NPs conjugation with ligands, which specifically deliver NPs to target cells via receptor binding. One such example is epidermal growth factor (EGF), a peptide involved in cell signaling pathways that control cell division by binding to epidermal growth factor receptor (EGFR). However, very few studies assessed the influence of EGF present in the cell environment, on the cellular uptake of NPs. Methods: We tested if the stimulation of EGFR-expressing lung carcinomacells A549 with EGF affects the uptake of 59 nm and 422 nm silica (SiO2) NPs. Additionally, we investigated whether the uptake enhancement can be achieved with gold NPs, suitable to downregulate the expression of cancer oncogene c-MYC. Results: Our findings show that EGF binding to its receptor results in receptor autophosphorylation and initiate signaling pathways, leading to enhanced endocytosis of 59 nm SiO2 NPs, but not 422 nm SiO2 NPs. Additionally, we demonstrated an enhanced gold (Au) NPs endocytosis and subsequently a higher downregulation of c-MYC. Discussion: These findings contribute to a better understanding of NPs uptake in the presence of EGF and that is a promising approach for improved NPs delivery.

Notes:

Funding Information: info:eu-repo/grantAgreement/FCT/3599-PPCDT/2022.04315.PTDC/PT# info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT# info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT# info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0140%2F2020/PT# info:eu-repo/grantAgreement/FCT/OE/2020.07660.BD/PT# The authors would like to acknowledge the financial support of the NCCR Bioinspired Materials through the Swiss National Science Foundation, the Adolphe Merkle Foundation. Aura Maria Moreno-Echeverri and Barbara Rothen-Rutishauser acknowledge the Swiss National Science Foundation (SNSF) (project 310030_192056/1). Publisher Copyright: Copyright © 2023 Susnik, Bazzoni, Taladriz-Blanco, Balog, Moreno-Echeverri, Glaubitz, Brito Oliveira, Ferreira, Viana Baptista, Petri-Fink and Rothen-Rutishauser.