TY - JOUR
T1 - Rod-shape theranostic nanoparticles facilitate antiretroviral drug biodistribution and activity in human immunodeficiency virus susceptible cells and tissues
AU - Kevadiya, Bhavesh D.
AU - Ottemann, Brendan
AU - Mukadam, Insiya Z.
AU - Castellanos, Laura
AU - Sikora, Kristen
AU - Hilaire, James R.
AU - Machhi, Jatin
AU - Herskovitz, Jonathan
AU - Soni, Dhruvkumar
AU - Hasan, Mahmudul
AU - Zhang, Wenting
AU - Anandakumar, Sarella
AU - Garrison, Jered
AU - McMillan, Jo Ellyn
AU - Edagwa, Benson
AU - Mosley, R. Lee
AU - Vachet, Richard W.
AU - Gendelman, Howard E.
N1 - Funding Information:
The authors are grateful to the National Isotope Development Center, Oak Ridge National Laboratory, Oak Ridge, TN, USA, for providing 177LuCl3. The authors would like to thank Janice A. Taylor and James R. Talaska of the Advanced Microscopy Core Facility at the UNMC for helping with confocal microscopy. We also would like to thank Drs. Alexander Lushnikov and Alexey Krasnoslobodtsev for assistance during AFM imaging at the Nanoimaging Core Facility of the UNMC. The authors thank to Drs. Shah Valloppilly and Bala Balasubramanian for XRD and XPS analyses. The research was performed in part in the Nebraska Nanoscale Facility: National Nanotechnology Coordinated Infrastructure and the Nebraska Center for Materials and Nanoscience, which are supported by the National Science Foundation under Award ECCS: 1542182, and the Nebraska Research Initiative. The authors would like to thank Nicholas Conoan of the Electron Microscopy Core Facility (EMCF) at the University of Nebraska Medical Center (UNMC) for his technical assistance. The authors are also thankful to Prof. You (Joe) Zhou for his contribution to SEM and TEM imaging and Dr. Javier Seravalli for ICP-MS analysis which were performed at the Center for Biotechnology, Redox Biology group at the University of Nebraska-Lincoln. The authors appreciate the excellent technical assistance made by Drs. Yutong Liu, Balasrinivasa R. Sajja and Yaman Lu in support of the initial SPECT data analysis. Bhagya Laxmi Dyavar Shetty and Melinda S. Wojtkiewicz performed the UPLC-MS/MS analysis of RPV in tissue and plasma, while Dr. Prasanta Dash and Sruthi Sravananm assisted in tissue sectioning and slide preparations for histopathological analyses. The authors would also like to thank Dr. Josh Souchek for help with NIR imaging.
Publisher Copyright:
© The author(s).
PY - 2020
Y1 - 2020
N2 - Human immunodeficiency virus theranostics facilitates the development of long acting (LA) antiretroviral drugs (ARVs) by defining drug-particle cell depots. Optimal drug formulations are made possible based on precise particle composition, structure, shape and size. Through the creation of rod-shaped particles of defined sizes reflective of native LA drugs, theranostic probes can be deployed to measure particle-cell and tissue biodistribution, antiretroviral activities and drug retention. Methods: Herein, we created multimodal rilpivirine (RPV) 177lutetium labeled bismuth sulfide nanorods (177LuBSNRs) then evaluated their structure, morphology, configuration, chemical composition, biological responses and adverse reactions. Particle biodistribution was analyzed by single photon emission computed tomography (SPECT/CT) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging. Results: Nanoformulated RPV and BSNRs-RPV particles showed comparable physicochemical and cell biological properties. Drug-particle pharmacokinetics (PK) and biodistribution in lymphoid tissue macrophages proved equivalent, one with the other. Rapid particle uptake and tissue distribution were observed, without adverse reactions, in primary blood-derived and tissue macrophages. The latter was seen within the marginal zones of spleen. Conclusions: These data, taken together, support the use of 177LuBSNRs as theranostic probes as a rapid assessment tool for PK LA ARV measurements.
AB - Human immunodeficiency virus theranostics facilitates the development of long acting (LA) antiretroviral drugs (ARVs) by defining drug-particle cell depots. Optimal drug formulations are made possible based on precise particle composition, structure, shape and size. Through the creation of rod-shaped particles of defined sizes reflective of native LA drugs, theranostic probes can be deployed to measure particle-cell and tissue biodistribution, antiretroviral activities and drug retention. Methods: Herein, we created multimodal rilpivirine (RPV) 177lutetium labeled bismuth sulfide nanorods (177LuBSNRs) then evaluated their structure, morphology, configuration, chemical composition, biological responses and adverse reactions. Particle biodistribution was analyzed by single photon emission computed tomography (SPECT/CT) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging. Results: Nanoformulated RPV and BSNRs-RPV particles showed comparable physicochemical and cell biological properties. Drug-particle pharmacokinetics (PK) and biodistribution in lymphoid tissue macrophages proved equivalent, one with the other. Rapid particle uptake and tissue distribution were observed, without adverse reactions, in primary blood-derived and tissue macrophages. The latter was seen within the marginal zones of spleen. Conclusions: These data, taken together, support the use of 177LuBSNRs as theranostic probes as a rapid assessment tool for PK LA ARV measurements.
KW - Drug biodistribution
KW - Laser ablation inductively coupled plasma mass spectrometry
KW - Long acting antiretroviral therapy
KW - Multimodal imaging
KW - Single photon emission computed tomography
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U2 - 10.7150/thno.39847
DO - 10.7150/thno.39847
M3 - Article
C2 - 31903142
AN - SCOPUS:85076574661
SN - 1838-7640
VL - 10
SP - 630
EP - 656
JO - Theranostics
JF - Theranostics
IS - 2
ER -