Rilpivirine-associated aggregation-induced emission enables cell-based nanoparticle tracking. (February 2020)

• Record Type: Journal Article
• Authors: Mukadam, Insiya Z.; Machhi, Jatin; Herskovitz, Jonathan; Hasan, Mahmudul; Oleynikov, Maxim D.; Blomberg, Wilson R.; Svechkarev, Denis; Mohs, Aaron M.; Zhou, You; Dash, Prasanta; McMillan, JoEllyn; Gorantla, Santhi; Garrison, Jered; Gendelman, Howard E.; Kevadiya, Bhavesh D.
• Is Part Of: Biomaterials. Volume 231(2020)
• Publication Date: 2020-02
• Subjects: Rilpivirine -- Antiretroviral therapy -- Aggregation-induced emission -- Single-crystal x-ray diffraction -- CD4+ T cell tracking -- Monocyte-macrophage -- Drug biodistribution; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2019.119669
• Languages: English
• ISSNs: 0142-9612

Abstract

Graphical abstract: Image 1 Abstract: Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, limitations in drug efficacy, emergence of viral mutations and the paucity of cell-tissue targeting remain. We posit that to maximize ART potency and therapeutic outcomes newer drug formulations that reach HIV cellular reservoirs need be created. In a step towards achieving this goal we harnessed the aggregation-induced emission (AIE) property of the non-nucleoside reverse transcriptase inhibitor rilpivirine (RPV) and used it as a platform for drug cell and subcellular tracking. RPV nanocrystals were created with endogenous AIE properties enabling the visualization of intracellular particles in cell and tissue-based assays. The intact drug crystals were easily detected in CD4 + T cells and macrophages, the natural viral target cells, by flow cytometry and ultraperformance liquid chromatography tandem mass spectrometry. We conclude that AIE can be harnessed to monitor cell biodistribution of selective antiretroviral drug nanocrystals. Highlights: Rilpivirine (RPV) demonstrates aggregation-induced emission. RPV nanocrystals are produced by a combination of bottom up plus top down methods. Single-crystal x-ray crystallography data reveal CH-π interactions leading to restricted intramolecular rotations. RPV nanocrystals are observed in CD14 + macrophages and CD4 + T-cells as detected by confocal microscopy. Nanoparticle tracking is operative in human immunodeficiency virus infectious reservoirs.