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Title:Development of a click chemistry approach for cancer cell targeting and evaluating the effect of protein corona on active targeting yield
Author(s):Mirshafiee, Vahid
Advisor(s):Kraft, Mary L.
Department / Program:Chemical & Biomolecular Engr
Discipline:Chemical Engineering
Degree Granting Institution:University of Illinois at Urbana-Champaign
Targeted Drug Delivery
Click Chemistry
Protein Corona
Abstract:The routine approach for targeting nanoparticle delivery vehicles to cancer cells is by incorporating targeting ligands (e.g. antibodies or aptamers) to the surface of nanoparticles (NPs). Although targeting ligands are known to interact with specific receptors in the membranes of cancer cells, resulting in enhanced NP uptake, these functionalized NPs have an undesirable biodistribution and unfavorable targeting efficacy. Here we demonstrate a novel approach to target NPs to the cancer cells via click chemistry. Cancer cells are first metabolically labeled with an azide-modified monosaccharide (azidosugar). In the second step, NPs that are functionalized with highly-reactive cycloalkynes selectively bind to the cancer cells due to a spontaneous click reaction between the cycloalkynes on NP’s surfaces and the metabolically incorporated azide groups in the cell membranes. Our results show that HeLa and Chinese hamster ovary (CHO) cells are successfully labeled with azidosugars, and cycloalkyne-functionalized silica NPs bind to the metabolically labeled cells via the click reaction. The click chemistry reaction was also used to study the effect of protein adsorption on active NP targeting. Upon exposure of NPs to the biological environment, proteins and other biomolecules bind to the NPs and cover their surfaces. This protein coating, which is called the protein corona, may reduce the targeting capability of functionalized NPs by screening their targeting ligands. Here we used cycloalkyne-functionalized silica NPs that can bind to the azide-modified silicon substrates to study this effect. The results demonstrate that the formation of protein corona significantly decreased the conjugation of functionalized NPs to the substrate.
Issue Date:2013-05-28
Rights Information:Copyright 2013 Vahid Mirshafiee
Date Available in IDEALS:2013-05-28
Date Deposited:2013-05

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