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

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 lutetium 177 -doped EuS ( 177 LuEuS) 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.

CCR5 Decorated Rilpivirine Lipid Nanoparticles Build Myeloid Drug Depots Which Sustains Antiretroviral Activities

“…This tri-modality was selected based on known safety and ease in biological monitoring. 12 , 13 The chelator-free 64 CuInEuS 2 nanoprobe was synthesized by solvothermal methods using thioacetamide, europium (III) chloride hexahydrate, indium (III) chloride dihydrate, and copper (II) chloride dihydrate at optimal molar ratios. The high boiling solvent, oleylamine, was selected for solvothermal synthesis to avoid narrowly dispersed particles.…”

“…However, this alone may not allow drug accumulation to viral reservoirs. 13 Success is made by optimizing antiretroviral drug (ARV) tissue and cell-specific targeting. LNPs may improve ARV pharmacodynamics by increasing drug circulation time and bioavailability.…”