DigitalCommons@UNMC

Title

Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution

Authors

Bhavesh D. Kevadiya, University of Nebraska Medical CenterFollow
Christopher J. Woldstad, University of Nebraska Medical CenterFollow
Brendan M. Ottemann, University of Nebraska Medical CenterFollow
Prasanta Dash, University of Nebraska Medical CenterFollow
Balasrinivasa R. Sajja, University of Nebraska Medical CenterFollow
Benjamin G. Lamberty, University of Nebraska Medical CenterFollow
Brenda M. Morsey, University of Nebraska Medical CenterFollow
Ted Kocher, University of Nebraska Medical Center
Rinku Dutta, University of Nebraska Medical CenterFollow
Aditya N. Bade, University of Nebraska Medical CenterFollow
Yutong Liu, University of Nebraska Medical CenterFollow
Shannon E. Callen, University of Nebraska Medical CenterFollow
Howard S. Fox, University of Nebraska Medical CenterFollow
Siddappa N. Byrareddy, University of Nebraska Medical CenterFollow
JoEllyn M. McMillan, University of Nebraska Medical Center, OmahaFollow
Tatiana K. Bronich, University of Nebraska Medical CenterFollow
Benson J. Edagwa, University of Nebraska Medical Center, OmahaFollow
Michael D. Boska, University of Nebraska Medical Center
Howard Gendelman, University of Nebraska Medical Center & Nebraska Center for VirologyFollow

Document Type

Article

Journal Title

Theranostics

Publication Date

2017

Volume

8

Abstract

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models.

METHODS: Europium (Eu³⁺)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution.

RESULTS: Folic acid (FA) decoration of EuCF-DTG (FA-EuCF-DTG) nanoparticles facilitated macrophage targeting and sped drug entry across cell barriers. Macrophage uptake was higher for FA-EuCF-DTG than EuCF-DTG nanoparticles with relaxivities of r₂ = 546 mM^-1s^-1 and r₂ = 564 mM^-1s^-1 in saline, and r₂ = 850 mM^-1s^-1 and r₂ = 876 mM^-1s^-1 in cells, respectively. The values were ten or more times higher than what was observed for ultrasmall superparamagnetic iron oxide particles (r₂ = 31.15 mM^-1s^-1 in saline) using identical iron concentrations. Drug particles were detected in macrophage Rab compartments by dual fluorescence labeling. Replicate particles elicited sustained antiretroviral responses. After parenteral injection of FA-EuCF-DTG and EuCF-DTG into rats and rhesus macaques, drug, iron and cobalt levels, measured by LC-MS/MS, magnetic resonance imaging, and ICP-MS were coordinate.

CONCLUSION: We posit that these theranostic nanoprobes can assess LASER ART drug delivery and be used as part of a precision nanomedicine therapeutic strategy.

DOI Link

10.7150/thno.22764

ISSN

18387640

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Kevadiya, Bhavesh D.; Woldstad, Christopher J.; Ottemann, Brendan M.; Dash, Prasanta; Sajja, Balasrinivasa R.; Lamberty, Benjamin G.; Morsey, Brenda M.; Kocher, Ted; Dutta, Rinku; Bade, Aditya N.; Liu, Yutong; Callen, Shannon E.; Fox, Howard S.; Byrareddy, Siddappa N.; McMillan, JoEllyn M.; Bronich, Tatiana K.; Edagwa, Benson J.; Boska, Michael D.; and Gendelman, Howard, "Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution" (2017). Journal Articles: Radiology. 9.
https://digitalcommons.unmc.edu/com_xray_articles/9