Investigating the Interactions of Self-Organized Nanoparticles with the Immune System

Nanotechnology, with its widespread applications, holds particular significance in healthcare. Engineered nanomaterials, exploiting unique properties at the nanoscale, present enhanced surface area and novel characteristics, making them invaluable in various medical applications. These encompass improved drug solubility, advanced drug delivery systems, cellular and tissue repair, diagnostic tools, and therapeutic medicines. Despite their potential benefits, the introduction of nanomaterials introduces new toxicological risks, necessitating a thorough understanding and monitoring of their bioavailability, bioaccumulation, toxicity, and environmental interactions. The full therapeutic potential of nanomedicine relies on overcoming challenges like interactions with the body's defenses and adverse immune reactions. Understanding the nanomaterials-host interplay is crucial, and this project aims to shed light on the protein corona formation—a critical process in nano-bio interactions. In this PhD thesis, various nanoparticles, including silica-based nanoparticles, polymeric nanoparticles, and gold nanoparticles, were explored for their potential applications in medicine. The primary goal was to introduce new biocompatible nanomaterials capable of enhancing conventional therapies while gaining a better understanding of their properties and behavior in humans. The research initially focuses on studying the interaction of Ficolins using monolayer-protected gold nanoparticles as a model. The uptake depends on the charged headgroup or the amino acids present in the monolayer. Modified molecules, influenced by acetyl or propionyl groups on the nanoparticle surface, were examined. Preliminary results indicate the affinity of Ficolins with propionylated residues, suggesting a novel recognition pathway. The investigation then delves into the immune system's response to foreign substances, utilizing silica-based nanoparticles coated with poly-oxazoline-based polymers as nano vectors. These nanoparticles, serving as a platform for conjugating peptides, show promise in inducing an immune response that activates adaptive immunity, such as T-cells, to combat cancer. However, further optimization studies are required due to the charge of the peptides. Finally, the study focuses on polymeric nanoparticles based on poly(disulfide)s for their potential application in RNA delivery. Modifications, such as changing the coating to phospholipids or polymers, were explored, along with the development of a new precursor conjugating cholesterol and lipoic acid. Preliminary results studying the formation of the protein corona and uptake by dendritic cells aim to evaluate the bio interaction of these new classes of nanoparticles.