Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy

  • Nouf Alsharif

Student thesis: Doctoral Thesis

Abstract

The innovation of multifunctional efficient, and safer treatments is a major challenge in nanomedicine. For example, the combination of magneto-mechanical and the photothermal strategies into one single therapeutic stage is one of the promising developments in cancer treatment. Without specificity, however, these therapies would target and harm both cancer and healthy cells. Therefore, the goal of precision medicine is to focus on delivering therapies to specific cells and minimize the side effects on healthy. Therefore, in this study, biocompatible, magnetic iron nanowires were functionalized with antibodies directed against CD44, a cell surface marker that is overexpressed in a large number of cancer cells. To test the functionality of the antibodies following conjugation to the iron nanowires, immunostaining and immunoprecipitation were performed and confirmed that the antigenicity of the antibodies was preserved following their conjugation to the nanowires. Indeed, the antibody coated nanowires were shown to play a major role in enhancing the accumulation and the internalization of nanowires to the cell surface in both adherent cells (e.g. colon cancer cells) and suspension cells (e.g., leukemia cells). Moreover, inductively coupled plasma mass spectrometry was used to quantify the attached and internalized nanowires. After only 1 h, the presence of antibodies enhanced the ability of the NWs to specifically target cancer cells, by more than 60% in both colon and leukemic cancers, compared to their negative controls. In addition, the presence of antibodies did not affect the magnetization of the nanowires. Therefore, the combination of both magneto-mechanical and photothermal strategies in the presence of the antibodies functionalized nanowires was applied to two types of cancer cells, colon cancer and leukemia. Strikingly, the targeted nanowires resulted in more than 76±3.5% and 45.5±0.4% cell death of colon cancer and leukemic target cells and less than 40% of cells died from the non-targeted NWs. These results represent a significant finding, as this is the first study which examines the role antibodies play in the internalization of iron nanowires, and more importantly, the efficacy to kill cancer cells. It also confirmed the possibility of targeting cancer cells with functionalized nanowires and destroying these cells utilizing combined strategies.
Date of AwardOct 2019
Original languageEnglish (US)
Awarding Institution
  • Biological, Environmental Science and Engineering
SupervisorJurgen Kosel (Supervisor)

Keywords

  • Nanowires
  • Antibody
  • Targeting
  • Magnetomechanical
  • Photothermal
  • Cancer-therpy

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