Development of a click chemistry approach for cancer cell targeting and evaluating the effect of protein corona on active targeting yield
Mirshafiee, Vahid
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https://hdl.handle.net/2142/44777
Description
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
Issue Date
2013-05-28T19:19:29Z
Director of Research (if dissertation) or Advisor (if thesis)
Kraft, Mary L.
Department of Study
Chemical & Biomolecular Engr
Discipline
Chemical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(s)
Nanoparticle
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.
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