Targeted human serum albumin nanoparticles for specific uptake in EGFR-Expressing colon carcinoma cells

doi:10.1016/j.nano.2010.12.003

Nanomedicine: Nanotechnology, Biology and Medicine

Volume 7, Issue 4, August 2011, Pages 454-463

https://doi.org/10.1016/j.nano.2010.12.003 Get rights and content

Abstract

The specific application and transport of drugs into malignant tissue is a critical point during diagnosis and therapy. Nanoparticles are known as excellent drug carrier systems and offer the possibility of surface modification with targeting ligands, leading to a specific accumulation in the targeted tissue. First, the specificity of such a carrier system has to be proven. In this study, cetuximab-modified nanoparticles based on biodegradable human serum albumin (HSA) are investigated regarding their cellular binding and intracellular accumulation. Different EGFR-expressing colon carcinoma cells were used to test possible cytotoxic potential, specific binding and intracellular accumulation. A specific accumulation targeting the EGFR could be shown. These results emphasize that cetuximab-modified HSA-nanoparticles are a promising carrier system for later drug transport. To our knowledge, this is the first study investigating the specific accumulation of HSA nanoparticles into different EGFR-expressing colon carcinoma cells.

From the Clinical Editor

In this study, cetuximab-modified nanoparticles based on human serum albumin (HSA) are investigated regarding their cellular binding and intracellular accumulation. The results suggest that these nanoparticles are a promising carrier system for EGFR overexpressing colon carcinoma cells.

Graphical Abstract

Specific cellular accumulation of cetuximab-modified nanoparticles based on human serum albumin in different EGFR-expressing colon carcinoma cell lines. HSA-cetuximab nanoparticles show a cell specific accumulation depending the cellular EGFR-expression.

Section snippets

Methods

Detailed information on materials, nanoparticle preparation and characterization, and statistical analysis can be found in the Supplementary Methods, available in the online version of this article.

Preparation of cetuximab-modified HSA-nanoparticles

The HSA-nanoparticles were prepared by desolvation technique followed by covalent conjugation with the antibody via a PEG cross linker (Supplementary Information, Figure S1). An unspecific IgG antibody and a monofunctional mPEG reagent were used as controls for cell-culture experiments. The particles showed a size between 200 and 250 nanometers and an antibody loading of 20.8 ± 1.9 μg/mg for cetuximab and 16.7 ± 2.8 μg/mg for IgG, respectively (Table 1).

Characterization of EGFR expression

The EGFR expression of the two studied

Discussion

Specific targeting of malignant tissue for diagnosis and therapy is one of the major goals in recent nanotechnology. The use of specific modified nanoparticles offers the possibility of efficient drug transport and application into the targeted tissue. A wide range of ligands is used for the modification of nanoparticles. Predominantly, mAb are taken as targeting ligands.¹⁹ The humanized IgG1 monoclonal antibody cetuximab (Erbitux) is directed against the EGFR, which is highly over-expressed in

Acknowledgment

We would also like to thank PD Dr. K. David from Indivumed for providing the LS174T cells.

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: This work was supported by the German Federal Ministry of Education and Research BMBF in the context of the Research Project NanoCancer (Contract number: 0312026).

: The authors acknowledge Bundesministerium für Bildung und Forschung (BMBF); project 0312026A for financial support.

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Research ArticleTargeted human serum albumin nanoparticles for specific uptake in EGFR-Expressing colon carcinoma cells

Abstract

From the Clinical Editor

Graphical Abstract

Section snippets

Methods

Preparation of cetuximab-modified HSA-nanoparticles

Characterization of EGFR expression

Discussion

Acknowledgment

Urol Oncol

Adv Drug Deliv Rev

Adv Drug Deliv Rev

Urol Oncol

J Control Release

Int J Pharm

J Control Release

Microvasc Res

Biomaterials

Clin Ther

Crit Rev Oncol Hematol

Int J Pharm

Int J Pharm

Biomaterials

Int J Pharm

Cancer Lett

Trends Biotechnol

Research Article
Targeted human serum albumin nanoparticles for specific uptake in EGFR-Expressing colon carcinoma cells