Multicolor Polymeric Nanoparticle Neuronal Tracers

Nanzhi Zang; John B Issa; Treffly B Ditri; Dante S Bortone; Mollie A Touve; Anthony M Rush; Massimo Scanziani; Daniel A Dombeck; Nathan C Gianneschi

doi:10.1021/acscentsci.0c00027

Multicolor Polymeric Nanoparticle Neuronal Tracers

ACS Cent Sci. 2020 Mar 25;6(3):436-445. doi: 10.1021/acscentsci.0c00027. Epub 2020 Feb 24.

Authors

Nanzhi Zang¹, John B Issa², Treffly B Ditri³, Dante S Bortone⁴, Mollie A Touve¹, Anthony M Rush³, Massimo Scanziani^{4

5}, Daniel A Dombeck², Nathan C Gianneschi^{1

6

3}

Affiliations

¹ Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.
² Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, United States.
³ Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, California 92093, United States.
⁴ Department of Neurobiology, University of California, San Diego, La Jolla, California 92093, United States.
⁵ Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143, United States.
⁶ Department of Materials Science & Engineering, Department of Biomedical Engineering, Department of Pharmacology, International Institute of Nanotechnology, Chemistry of Life Processes Institute, Simpson Querrey Institute, Northwestern University, Evanston, Illinois 60208, United States.

Abstract

Deciphering the targets of axonal projections plays a pivotal role in interpreting neuronal function and pathology. Neuronal tracers are indispensable tools for uncovering the functions and interactions between different subregions of the brain. However, the selection of commercially available neuronal tracers is limited, currently comprising small molecule dyes, viruses, and a handful of synthetic nanoparticles. Here, we describe a series of polymer-based nanoparticles capable of retrograde transport along neurons in vivo in mice. These polymeric nanoparticle neuronal tracers (NNTs) are prepared with a palette of fluorescent labels. The morphologies, charges, and optical properties of NNTs are characterized by analytical methods including fluorescence microscopy, electron microscopy, and dynamic light scattering. Cytotoxicity and cellular uptake were investigated to analyze cellular interactions in vitro. Regardless of the type of fluorophore used in labeling, each tracer was of similar morphology, size, and charge and was competent for retrograde transport in vivo. The platform provides a convenient, scalable synthetic approach for nonviral tracers labeled with a range of fluorophores for in vivo neuronal projection mapping.