Europium sulfide nanoprobes predict antiretroviral drug delivery into HIV-1 cell and tissue reservoirs

Jonathan Herskovitz, Mahmudul Hasan, Jatin Machhi, Insiya Mukadam, Brendan M. Ottemann, James R. Hilaire, Christopher Woldstad, Jo Ellyn McMillan, Yutong Liu, Javier Seravalli, Anandakumar Sarella, Howard E. Gendelman, Bhavesh D. Kevadiya

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Delivery of long-acting nanoformulated antiretroviral drugs (ARVs) to human immunodeficiency virus type one cell and tissue reservoirs underlies next generation antiretroviral therapeutics. Nanotheranostics, comprised of trackable nanoparticle adjuncts, can facilitate ARV delivery through real-time drug tracking made possible through bioimaging platforms. Methods: To model HIV-1 therapeutic delivery, europium sulfide (EuS) nanoprobes were developed, characterized and then deployed to cells, tissues, and rodents. Tests were performed with nanoformulated rilpivirine (NRPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used clinically to suppress or prevent HIV-1 infection. First, CD4+ T cells and monocyte-derived macrophages were EuS-treated with and without endocytic blockers to identify nanoprobe uptake into cells. Second, Balb/c mice were co-dosed with NRPV and EuS or lutetium177-doped EuS (177LuEuS) theranostic nanoparticles to assess NRPV biodistribution via mass spectrometry. Third, single photon emission computed tomography (SPECT-CT) and magnetic resonance imaging (MRI) bioimaging were used to determine nanotheranostic and NRPV anatomic redistribution over time. Results: EuS nanoprobes and NRPV entered cells through dynamin-dependent pathways. SPECT-CT and MRI identified biodistribution patterns within the reticuloendothelial system for EuS that was coordinate with NRPV trafficking. Conclusions: EuS nanoprobes parallel the uptake and biodistribution of NRPV. These data support their use in modeling NRPV delivery to improve treatment strategies.

Original languageEnglish (US)
Pages (from-to)417-430
Number of pages14
JournalNanotheranostics
Volume5
Issue number4
DOIs
StatePublished - 2021

Keywords

  • HIV-1
  • SPECT-CT
  • antiretroviral
  • europium
  • molecular imaging
  • nanotheranostics

ASJC Scopus subject areas

  • Biotechnology
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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