Modified Antibody for Targeted Drug Delivery and Reduced Immunogenicity

Bibliographic Details
Main Author: Badkas, Apurva H.
Language:English
Published: University of Cincinnati / OhioLINK 2014
Subjects:
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407410100
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin14074101002021-08-03T06:26:57Z Modified Antibody for Targeted Drug Delivery and Reduced Immunogenicity Badkas, Apurva H. Chemical Engineering Drug Delivery Immunogenicity NP-Protein Modification Traditional cancer therapies suffer from toxicity, lack of selectivity, and resistance to drugs. In order to increase the dose reaching the tumor tissue, targeted therapeutic approach is being used. Nanoparticles (NPs) can carry larger amount of drugs, however the amount of these NP systems reaching is less than 10%. Most of these NPs get taken up by cells of the immune system, and segregate in organs of the body such as liver, lungs and spleen. Adding a polymer coating such as Poly ethylene glycol reduces the non-specific uptake. Adding a targeting ligand on the NP surface allows specific interaction with the tumor target and intracellular delivery of the payload. However, the protein coating covers the PEG surface. This study undertakes modification of the antibody of interest (Herceptin) with short PEG moieties. It deals with the characterization of the plain and modified Herceptin and immune response of the mouse macrophage cell line RAW 264.7 to NP-antibody/ NP-modified antibody system. Herceptin and modified Herceptin were characterized using Matrix Assisted Laser Desorption/ Ionization (MALDI) and Mass Spectrometry. Two cytokines, TNF-a and IL-1ß were measured by Enzyme Linked Immuno Sorbent Assay (ELISA). Fluorescent Microscopy study was undertaken. Systematic study of the applicability of the Bradford Assay to the modified antibody was done. Two standard proteins: Bovine Serum Albumin (BSA) and Bovine Gamma Globulin (BGG) were compared with Herceptin response. Modeling of the Herceptin structure was done using the protein sequence available in the Protein databank. 2014-10-10 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407410100 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407410100 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Chemical Engineering
Drug Delivery
Immunogenicity
NP-Protein
Modification
spellingShingle Chemical Engineering
Drug Delivery
Immunogenicity
NP-Protein
Modification
Badkas, Apurva H.
Modified Antibody for Targeted Drug Delivery and Reduced Immunogenicity
author Badkas, Apurva H.
author_facet Badkas, Apurva H.
author_sort Badkas, Apurva H.
title Modified Antibody for Targeted Drug Delivery and Reduced Immunogenicity
title_short Modified Antibody for Targeted Drug Delivery and Reduced Immunogenicity
title_full Modified Antibody for Targeted Drug Delivery and Reduced Immunogenicity
title_fullStr Modified Antibody for Targeted Drug Delivery and Reduced Immunogenicity
title_full_unstemmed Modified Antibody for Targeted Drug Delivery and Reduced Immunogenicity
title_sort modified antibody for targeted drug delivery and reduced immunogenicity
publisher University of Cincinnati / OhioLINK
publishDate 2014
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407410100
work_keys_str_mv AT badkasapurvah modifiedantibodyfortargeteddrugdeliveryandreducedimmunogenicity
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