Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles

Álamo, Patricia; Pallarès, Victor; Céspedes, María Virtudes; Falgàs, Aïda; Sanchez, Julieta M.; Serna, Naroa; Sánchez-García, Laura; Voltà-Duràn, Eric; Morris, Gordon A.; Sánchez-Chardi, Alejandro; Casanova, Isolda; Mangues, Ramón; Vazquez, Esther; Villaverde, Antonio; Unzueta, Ugutz

doi:10.3390/pharmaceutics12111004

Open AccessArticle

Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles

by

Patricia Álamo

^1,2,3,†,

Victor Pallarès

^1,2,3,†

,

María Virtudes Céspedes

^1,2,

Aïda Falgàs

^1,2,3,

Julieta M. Sanchez

^4,5,6,

Naroa Serna

^2,4,5,

Laura Sánchez-García

^2,4,5,

Eric Voltà-Duràn

^2,4,5

,

Gordon A. Morris

⁷

,

Alejandro Sánchez-Chardi

^8,9

,

Isolda Casanova

^1,2,3,

Ramón Mangues

^1,2,3,*

,

Esther Vazquez

^2,4,5

,

Antonio Villaverde

^2,4,5,*

and

Ugutz Unzueta

^1,2,3,5,*

¹

Biomedical Research Institute Sant Pau (IIB Sant Pau), Sant Antoni Mª Claret 167, 08025 Barcelona, Spain

²

CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3–5, 28029 Madrid, Spain

³

Josep Carreras Leukaemia Research Institute (IJC Campus Sant Pau), 08025 Barcelona, Spain

⁴

Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain

⁵

Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain

⁶

ICTA & Cátedra de Química Biológica, Departamento de Química, Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT) (CONICET—Universidad Nacional de Córdoba), FCEFyN, UNC. Av. Velez Sarsfield 1611, X 5016GCA Córdoba, Argentina

⁷

Department of Chemical Sciences, School of Applied Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK

⁸

Servei de Microscòpia, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain

⁹

Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain

^*

Authors to whom correspondence should be addressed.

^†

These authors contribute equally to this paper.

Pharmaceutics 2020, 12(11), 1004; https://doi.org/10.3390/pharmaceutics12111004

Submission received: 26 September 2020 / Revised: 16 October 2020 / Accepted: 20 October 2020 / Published: 22 October 2020

(This article belongs to the Special Issue Self-Assembling Smart Nanoparticles for Drug Delivery)

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Abstract

Fluorescent dye labeling is a common strategy to analyze the fate of administered nanoparticles in living organisms. However, to which extent the labeling processes can alter the original nanoparticle biodistribution has been so far neglected. In this work, two widely used fluorescent dye molecules, namely, ATTO488 (ATTO) and Sulfo-Cy5 (S-Cy5), have been covalently attached to a well-characterized CXCR4-targeted self-assembling protein nanoparticle (known as T22-GFP-H6). The biodistribution of labeled T22-GFP-H6-ATTO and T22-GFP-H6-S-Cy5 nanoparticles 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 accumulated mostly and specifically in CXCR4+ tumor cells, labeled T22-GFP-H6-ATTO and T22-GFP-H6-S-Cy5 nanoparticles showed a dramatic change in the biodistribution pattern, accumulating in non-target organs such as liver or kidney while reducing tumor targeting capacity. Therefore, the use of such labeling molecules should be avoided in target and non-target tissue uptake studies during the design and development of targeted nanoscale drug delivery systems, since their effect over the fate of the nanomaterial can lead to considerable miss-interpretations of the actual nanoparticle biodistribution.

Keywords: protein nanomaterials; functional materials; self-assembling nanoparticles; fluorescent labeling; biodistribution; targeting

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MDPI and ACS Style

Álamo, P.; Pallarès, V.; Céspedes, M.V.; Falgàs, A.; Sanchez, J.M.; Serna, N.; Sánchez-García, L.; Voltà-Duràn, E.; Morris, G.A.; Sánchez-Chardi, A.; et al. Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles. Pharmaceutics 2020, 12, 1004. https://doi.org/10.3390/pharmaceutics12111004

AMA Style

Álamo P, Pallarès V, Céspedes MV, Falgàs A, Sanchez JM, Serna N, Sánchez-García L, Voltà-Duràn E, Morris GA, Sánchez-Chardi A, et al. Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles. Pharmaceutics. 2020; 12(11):1004. https://doi.org/10.3390/pharmaceutics12111004

Chicago/Turabian Style

Álamo, Patricia, Victor Pallarès, María Virtudes Céspedes, Aïda Falgàs, Julieta M. Sanchez, Naroa Serna, Laura Sánchez-García, Eric Voltà-Duràn, Gordon A. Morris, Alejandro Sánchez-Chardi, and et al. 2020. "Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles" Pharmaceutics 12, no. 11: 1004. https://doi.org/10.3390/pharmaceutics12111004

APA Style

Álamo, P., Pallarès, V., Céspedes, M. V., Falgàs, A., Sanchez, J. M., Serna, N., Sánchez-García, L., Voltà-Duràn, E., Morris, G. A., Sánchez-Chardi, A., Casanova, I., Mangues, R., Vazquez, E., Villaverde, A., & Unzueta, U. (2020). Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles. Pharmaceutics, 12(11), 1004. https://doi.org/10.3390/pharmaceutics12111004

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Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles

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