Aptamer micelles targeting fractalkine-expressing cancer cells in vitro and in vivo

Michael A Harris; Timothy R Pearce; Thomas Pengo; Huihui Kuang; Colleen Forster; Efrosini Kokkoli

doi:10.1016/j.nano.2017.08.020

Aptamer micelles targeting fractalkine-expressing cancer cells in vitro and in vivo

Nanomedicine. 2018 Jan;14(1):85-96. doi: 10.1016/j.nano.2017.08.020. Epub 2017 Sep 11.

Authors

Michael A Harris¹, Timothy R Pearce², Thomas Pengo³, Huihui Kuang¹, Colleen Forster⁴, Efrosini Kokkoli⁵

Affiliations

¹ Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, USA.
² Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
³ University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN, USA.
⁴ BioNet, Academic Health Center, University of Minnesota, Minneapolis, MN, USA.
⁵ Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, USA. Electronic address: [email protected].

PMID: 28912042
DOI: 10.1016/j.nano.2017.08.020

Abstract

In this work we hypothesized that the chemokine fractalkine can serve as a cancer molecular target. We engineered aptamer micelles functionalized with an outer poly(ethylene glycol) (PEG) corona, and investigated the extent and efficacy of using them as a targeting tool against fractalkine-expressing colon adenocarcinoma cells. In vitro cell binding results showed that aptamer micelles bound and internalized to fractalkine-expressing cancer cells with the majority of the micelles found free in the cytoplasm. Minimal surface binding was observed by healthy cells. Even though partial PEGylation did not prevent serum adsorption, micelles were highly resistant to endonuclease and exonuclease degradation. In vivo biodistribution studies and confocal studies demonstrated that even though both aptamer and control micelles showed tumor accumulation, only the aptamer micelles internalized into fractalkine-expressing cancer cells, thus demonstrating the potential of the approach and showing that fractalkine may serve as a specific target for nanoparticle delivery to cancer cells.

Keywords: CX(3)CL1 chemokine; Colon cancer; Fractalkine; Targeted delivery; ssDNA aptamer micelles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / drug therapy*
Adenocarcinoma / metabolism
Adenocarcinoma / pathology
Animals
Aptamers, Nucleotide / administration & dosage*
Aptamers, Nucleotide / chemistry
Chemokine CX3CL1 / metabolism*
Colonic Neoplasms / drug therapy*
Colonic Neoplasms / metabolism
Colonic Neoplasms / pathology
Drug Carriers / chemistry
Drug Delivery Systems
Fibroblasts / drug effects*
Fibroblasts / metabolism
Fibroblasts / pathology
Humans
In Vitro Techniques
Mice
Micelles*
Polyethylene Glycols / chemistry
Tumor Cells, Cultured

Substances

Aptamers, Nucleotide
CX3CL1 protein, human
Chemokine CX3CL1
Drug Carriers
Micelles
Polyethylene Glycols