Design of Gold Nanoparticle-Based Drug Delivery Systems for Treating Inflammation-Associated Diseases

  • Fatima Ba Fakih

Student thesis: Master's Thesis

Abstract

Inflammation-associated diseases such as cardiovascular diseases, chronic obstructive pulmonary disease (COPD), and diabetes are the leading causes of death around the world. These diseases are associated with oxidative stress that is the overexpression of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2). ROS are mainly secreted by macrophages and they cause oxidative stress at the site of inflammation. Gold nanoparticles (AuNPs) constitute a promising drug delivery vehicle that offers an interesting set of tunable chemical and physical properties and they have no cytotoxic effects. In this study, we investigated the optimum size or shape of AuNPs that delivered catalase, an antioxidant enzyme that metabolises H2O2, to macrophages in oxidative stress. Ten different types of AuNPs were tested, including five spherical AuNPs with various sizes (50 nm, 80 nm, 100 nm, 200 nm, and 400 nm), and five shapes of AuNPs (cube, hexagon, bean, rod, and tetrapod). We demonstrated that catalase-conjugated AuNPs were not cytotoxic, can be uptaken by macrophages, reduce the level of ROS significantly, and enhance the viability of cells exposed to hydrogen peroxide. In particular, we showed that (1) catalase was easily conjugated to AuNPs, with rod and tetrapod AuNPs having the highest conjugation efficiency, (2) AuNPs were efficiently uptaken by RAW264.7 macrophages; spherical AuNPs were increasingly uptaken according to increased spherical size and cube, bean, and tetrapod shapes were the most uptaken AuNP shapes, (3) all shapes and three of the spherical AuNPs (80 nm, 100 nm, and 200 nm ) were able to significantly reduce the levels of ROS induced by the addition of H2O2. Among them, only 100 nm, 200 nm, hexagon AuNPs, bean AuNPs, and rod AuNPs were able to significantly increase the viability of cells under stress. However, bean AuNPs were superior to all. Taken together, these results indicate that catalase-conjugated AuNPs are an encouraging treatment modality targeting inflammation associated diseases.
Date of AwardJul 2020
Original languageAmerican English

Keywords

  • inflammation associated diseases
  • macrophages
  • reactive oxygen species
  • catalase
  • gold nanoparticles
  • and drug delivery.

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