Dye labeling for optical imaging biases drug carriers' biodistribution and tumor uptake

Sarah Schraven; Stefanie Rosenhain; Ramona Brueck; Tim Marvin Wiechmann; Robert Pola; Tomáš Etrych; Wiltrud Lederle; Twan Lammers; Felix Gremse; Fabian Kiessling

doi:10.1016/j.nano.2023.102650

Dye labeling for optical imaging biases drug carriers' biodistribution and tumor uptake

Nanomedicine. 2023 Feb:48:102650. doi: 10.1016/j.nano.2023.102650. Epub 2023 Jan 7.

Affiliations

¹ Institute for Experimental Molecular Imaging, RWTH Aachen University, Forckenbeckstrasse 55, 52074 Aachen, Germany.
² Institute for Experimental Molecular Imaging, RWTH Aachen University, Forckenbeckstrasse 55, 52074 Aachen, Germany; Gremse-IT GmbH, Dennewartstrasse 25, 52068 Aachen, Germany.
³ Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 06 Prague, Czech Republic.
⁴ Institute for Experimental Molecular Imaging, RWTH Aachen University, Forckenbeckstrasse 55, 52074 Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Fraunhofer MEVIS, Institute for Medical Image Computing, Aachen, Germany. Electronic address: fkiessling@ukaachen.de.

PMID: 36623712
DOI: 10.1016/j.nano.2023.102650

Abstract

Biodistribution analyses of nanocarriers are often performed with optical imaging. Though dye tags can interact with transporters, e.g., organic anion transporting polypeptides (OATPs), their influence on biodistribution was hardly studied. Therefore, this study compared tumor cell uptake and biodistribution (in A431 tumor-bearing mice) of four near-infrared fluorescent dyes (AF750, IRDye750, Cy7, DY-750) and dye-labeled poly(N-(2-hydroxypropyl)methacrylamide)-based nanocarriers (dye-pHPMAs). Tumor cell uptake of hydrophobic dyes (Cy7, DY-750) was higher than that of hydrophilic dyes (AF750, IRDye750), and was actively mediated but not related to OATPs. Free dyes' elimination depended on their hydrophobicity, and tumor uptake correlated with blood circulation times. Dye-pHPMAs circulated longer and accumulated stronger in tumors than free dyes. Dye labeling significantly influenced nanocarriers' tumor accumulation and biodistribution. Therefore, low-interference dyes and further exploration of dye tags are required to achieve the most unbiased results possible. In our assessment, AF750 and IRDye750 best qualified for labeling hydrophilic nanocarriers.

Keywords: Biodistribution; Drug delivery system; Fluorescent dye-labeling; Molecular imaging; Optical imaging.

Publication types

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

MeSH terms

Animals
Bias
Cell Line, Tumor
Drug Carriers* / chemistry
Fluorescent Dyes / chemistry
Mice
Neoplasms* / diagnostic imaging
Neoplasms* / drug therapy
Optical Imaging
Tissue Distribution

Substances

Drug Carriers
Fluorescent Dyes