Research Article

Zn-based physiometacomposite nanoparticles: distribution, tolerance, imaging, and antiviral and anticancer activity

Robert K DeLong

*Author for correspondence: +1 785 532 6313;

E-mail Address: robertdelong@ksu.edu

https://orcid.org/0000-0002-9568-7081

Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

Nanotechnology Innovation Center, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

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Ryan Swanson

Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

Nanotechnology Innovation Center, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

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Megan C Niederwerder

https://orcid.org/0000-0002-6894-1312

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

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Pratiksha Khanal

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

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Santosh Aryal

https://orcid.org/0000-0002-7807-6342

Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA

Department of Pharmaceutical Sciences and Health Outcomes, The Ben and Maytee Fisch College of Pharmacy, University of Texas at Tyler, Tyler, TX 75799, USA

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Ramesh Marasini

https://orcid.org/0000-0001-8905-2066

Nanotechnology Innovation Center, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA

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Majid Jaberi-Douraki

https://orcid.org/0000-0002-8505-6550

1DATA Consortium, & Department of Mathematics, Kansas State University Olathe, Olathe, KS 66061, USA

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Heman Shakeri

1DATA Consortium, & Department of Mathematics, Kansas State University Olathe, Olathe, KS 66061, USA

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Reza Mazloom

1DATA Consortium, & Department of Mathematics, Kansas State University Olathe, Olathe, KS 66061, USA

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Sarah Schneider

https://orcid.org/0000-0001-9063-8574

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA

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Steve Ensley

Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

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Lane L Clarke

https://orcid.org/0000-0002-4938-6261

Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211, USA

Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA

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Rowena A Woode

Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA

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Sarah Young

Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA

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Sagar Rayamajhi

https://orcid.org/0000-0001-5420-7873

Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA

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Tracy Miesner

Comparative Medicine Group, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

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Mary L Higginbotham

https://orcid.org/0000-0001-7655-6732

Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

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Zhoumeng Lin

https://orcid.org/0000-0002-8731-8366

Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

Institute for Computational Comparative Medicine, Kansas State University Manhattan, KS 66061, USA

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Tej Shrestha

Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

Nanotechnology Innovation Center, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

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Kartik Ghosh

Department of Physics, Astronomy & Materials Science, Missouri State University, Springfield, MO 65897, USA

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Garry Glaspell

US Army Corps of Engineers Engineer Research & Development Center, Alexandria, VA 22315, USA

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Elza N Mathew

https://orcid.org/0000-0002-4156-8183

Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA

University of Massachusetts Medical School, Worcester, MA 01605, USA

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Published Online:20 Jul 2021https://doi.org/10.2217/nnm-2021-0179

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Abstract

The aim of this study was to investigate the distribution, tolerance, and anticancer and antiviral activity of Zn-based physiometacomposites (PMCs). Manganese, iron, nickel and cobalt-doped ZnO, ZnS or ZnSe were synthesized. Cell uptake, distribution into 3D culture and mice, and biochemical and chemotherapeutic activity were studied by fluorescence/bioluminescence, confocal microscopy, flow cytometry, viability, antitumor and virus titer assays. Luminescence and inductively coupled plasma mass spectrometry analysis showed that nanoparticle distribution was liver >spleen >kidney >lung >brain, without tissue or blood pathology. Photophysical characterization as ex vivo tissue probes and LL37 peptide, antisense oligomer or aptamer delivery targeting RAS/Ras binding domain (RBD) was investigated. Treatment at 25 μg/ml for 48 h showed ≥98–99% cell viability, 3D organoid uptake, 3-log inhibition of β-Galactosidase and porcine reproductive respiratory virus infection. Data support the preclinical development of PMCs for imaging and delivery targeting cancer and infectious disease.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 16, No. 21

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History

Received 5 May 2021

Accepted 24 June 2021

Published online 20 July 2021

Published in print September 2021

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2021-0179

Acknowledgments

Some of the results/figures and some of the phrasing of the methods have been reproduced with permission from the dissertation of one of the authors (https://krex.k-state.edu/dspace/bitstream/handle/2097/40927/ElzaMathew2020.pdf?isAllowed=y&sequence=5).

Financial & competing interests disclosure

This work was supported by NSF RAPID grant (2029579) to RKD, MN and SA and CF Foundation Pilot award (CLARKE19XX0) to LC and RKD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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