Development of a protein nanoparticle platform for targeting EGFR expressing cancer cells

Buecheler, Jakob W., Howard, Christopher B., de Bakker, Christopher J., Goodall, Stephen, Jones, Martina L, Win, Thinzar, Peng, Tao, Tan, Cher Heng, Chopra, Akhil, Mahler, Stephen M and Lim, Sierin (2014) Development of a protein nanoparticle platform for targeting EGFR expressing cancer cells. Journal of Chemical Technology and Biotechnology, 90 7: 1230-1236. doi:10.1002/jctb.4545

Author Buecheler, Jakob W.
Howard, Christopher B.
de Bakker, Christopher J.
Goodall, Stephen
Jones, Martina L
Win, Thinzar
Peng, Tao
Tan, Cher Heng
Chopra, Akhil
Mahler, Stephen M
Lim, Sierin
Title Development of a protein nanoparticle platform for targeting EGFR expressing cancer cells
Journal name Journal of Chemical Technology and Biotechnology   Check publisher's open access policy
ISSN 0268-2575
Publication date 2014-10-27
Year available 2014
Sub-type Article (original research)
DOI 10.1002/jctb.4545
Open Access Status
Volume 90
Issue 7
Start page 1230
End page 1236
Total pages 7
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley and Sons
Collection year 2015
Language eng
Formatted abstract
A range of protein-based nanoparticles has been developed for cancer drug delivery and diagnostics. This includes the E2 protein derived from the pyruvate dehydrogenase complex in Geobacillus stearothermophilus which assembles into a 60-subunit protein cage structure that is capable of encapsulating cancer therapeutics. In this study antibody fragments targeting the epidermal growth factor receptor (EGFR) were tethered to the surface of E2 protein nanoparticles to determine whether the protein nanoparticles could be specifically targeted to EGFR overexpressing cancer cells.

Variants of the anti-EGFR antibody fragment and the E2 protein containing specific cysteine residues (E2ΔN17A186C) were conjugated using a maleimide-specific crosslinker. Electron microscopy and dynamic light scattering analysis indicated that the cysteine modified E2 protein correctly assembled into a 25–30 nm particle. The conjugation of the anti-EGFR antibody fragment (26 kDa) with a subunit of the E2 protein (26 kDa) was confirmed by mass spectrometry with an estimated molecular weight of 52 kDa. The binding of the conjugated E2 particle to native EGFR on MDA MB 231 cells and recombinant EGFR was confirmed using flow cytometry and biolayer interferometry, respectively.

In this study, proof-of-principle that an EGFR-targeting scFv can be stably conjugated to the cysteine variant E2ΔN17A186C protein nanoparticle without loss of targeting capability has been demonstrated. Conceptually scFv antibody fragments reactive with other important cancer targets could be utilized and presents the opportunity for generation of multi-targeted protein nanoparticles by conjugating various scFvs with different specificities on the same particle. © 2014 Society of Chemical Industry
Keyword Protein nanoparticle
Antibody targeting
Drug delivery
Cancer therapeutic
Epidermal growth factor receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Thu, 15 Jan 2015, 09:38:15 EST by Cathy Fouhy on behalf of Aust Institute for Bioengineering & Nanotechnology