Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy

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,...

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Main Author: Alsharif, Nouf
Other Authors: Kosel, Jürgen
Language:en
Published: 2019
Subjects:
Online Access:Alsharif, N. (2019). Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy. KAUST Research Repository. https://doi.org/10.25781/KAUST-56231
http://hdl.handle.net/10754/660354
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spelling ndltd-kaust.edu.sa-oai-repository.kaust.edu.sa-10754-6603542021-02-20T05:10:56Z Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy Alsharif, Nouf Kosel, Jürgen Biological and Environmental Sciences and Engineering (BESE) Division Merzaban, Jasmeen Blilou, Ikram Cortajarena, Aitziber López Nanowires Antibody Targeting Magnetomechanical Photothermal Cancer-therpy 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. 2019-12-02T09:27:10Z 2019-12-02T09:27:10Z 2019-10 Dissertation Alsharif, N. (2019). Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy. KAUST Research Repository. https://doi.org/10.25781/KAUST-56231 10.25781/KAUST-56231 http://hdl.handle.net/10754/660354 en 2020-08-26 At the time of archiving, the student author of this dissertation opted to temporarily restrict access to it. The full text of this dissertation became available to the public after the expiration of the embargo on 2020-08-26.
collection NDLTD
language en
sources NDLTD
topic Nanowires
Antibody
Targeting
Magnetomechanical
Photothermal
Cancer-therpy
spellingShingle Nanowires
Antibody
Targeting
Magnetomechanical
Photothermal
Cancer-therpy
Alsharif, Nouf
Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy
description 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.
author2 Kosel, Jürgen
author_facet Kosel, Jürgen
Alsharif, Nouf
author Alsharif, Nouf
author_sort Alsharif, Nouf
title Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy
title_short Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy
title_full Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy
title_fullStr Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy
title_full_unstemmed Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy
title_sort antibody-functionalized nanowires for active targeting and combination therapy
publishDate 2019
url Alsharif, N. (2019). Antibody-Functionalized Nanowires for Active Targeting and Combination Therapy. KAUST Research Repository. https://doi.org/10.25781/KAUST-56231
http://hdl.handle.net/10754/660354
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