Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles

PALLARÈS, VICTOR; SANCHEZ, JULIETA M.; VOLTÀ-DURÀN, ERIC; CASANOVA, ISOLDA; VILLAVERDE, ANTONIO; ÁLAMO, PATRICIA; FALGÀS, AÏDA; SÁNCHEZ-GARCÍA, LAURA; SÁNCHEZ-CHARDI, ALEJANDRO; VAZQUEZ, ESTHER; CÉSPEDES, MARÍA VIRTUDES; SERNA, NAROA; MORRIS, GORDON A.; MANGUES, RAMÓN; UNZUETA, UGUTZ

Pharmaceutics

MDPI

Año: 2020 vol. 12

Fluorescent dye labeling is a common strategy to analyze the fate of administerednanoparticles in living organisms. However, to which extent the labeling processes can alter theoriginal nanoparticle biodistribution has been so far neglected. In this work, two widely usedfluorescent dye molecules, namely, ATTO488 (ATTO) and Sulfo‐Cy5 (S‐Cy5), have been covalentlyattached to a well‐characterized CXCR4‐targeted self‐assembling protein nanoparticle (known asT22‐GFP‐H6). The biodistribution of labeled T22‐GFP‐H6‐ATTO and T22‐GFP‐H6‐S‐Cy5nanoparticles has been then compared to that of the non‐labeled nanoparticle in different CXCR4+tumor mouse models. We observed that while parental T22‐GFP‐H6 nanoparticles accumulatedmostly and specifically in CXCR4+ tumor cells, labeled T22‐GFP‐H6‐ATTO and T22‐GFP‐H6‐S‐Cy5nanoparticles showed a dramatic change in the biodistribution pattern, accumulating in non‐targetorgans such as liver or kidney while reducing tumor targeting capacity. Therefore, the use of suchlabeling molecules should be avoided in target and non‐target tissue uptake studies during thedesign and development of targeted nanoscale drug delivery systems, since their effect over the fateof the nanomaterial can lead to considerable miss‐interpretations of the actual nanoparticlebiodistribution.