Rilpivirine-associated aggregation-induced emission enables cell-based nanoparticle tracking

Insiya Z. Mukadam, Jatin Machhi, Jonathan Herskovitz, Mahmudul Hasan, Maxim D. Oleynikov, Wilson R. Blomberg, Denis Svechkarev, Aaron M. Mohs, You Zhou, Prasanta Dash, Jo Ellyn McMillan, Santhi Gorantla, Jered Garrison, Howard E. Gendelman, Bhavesh D. Kevadiya

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number119669
JournalBiomaterials
Volume231
DOIs
StatePublished - Feb 2020

Fingerprint

Rilpivirine
Nanoparticles
Agglomeration
Viruses
Nanocrystals
Pharmaceutical Preparations
Tissue
T-cells
Flow cytometry
Macrophages
Liquid chromatography
HIV
Cell Tracking
Drug Compounding
Reverse Transcriptase Inhibitors
Mass spectrometry
Assays
Virus Diseases
Visualization
Tandem Mass Spectrometry

Keywords

  • Aggregation-induced emission
  • Antiretroviral therapy
  • CD4 T cell tracking
  • Drug biodistribution
  • Monocyte-macrophage
  • Rilpivirine
  • Single-crystal x-ray diffraction

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Mukadam, I. Z., Machhi, J., Herskovitz, J., Hasan, M., Oleynikov, M. D., Blomberg, W. R., ... Kevadiya, B. D. (2020). Rilpivirine-associated aggregation-induced emission enables cell-based nanoparticle tracking. Biomaterials, 231, [119669]. https://doi.org/10.1016/j.biomaterials.2019.119669

Rilpivirine-associated aggregation-induced emission enables cell-based nanoparticle tracking. / 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, Jo Ellyn; Gorantla, Santhi; Garrison, Jered; Gendelman, Howard E.; Kevadiya, Bhavesh D.

In: Biomaterials, Vol. 231, 119669, 02.2020.

Research output: Contribution to journalArticle

Mukadam, IZ, Machhi, J, Herskovitz, J, Hasan, M, Oleynikov, MD, Blomberg, WR, Svechkarev, D, Mohs, AM, Zhou, Y, Dash, P, McMillan, JE, Gorantla, S, Garrison, J, Gendelman, HE & Kevadiya, BD 2020, 'Rilpivirine-associated aggregation-induced emission enables cell-based nanoparticle tracking', Biomaterials, vol. 231, 119669. https://doi.org/10.1016/j.biomaterials.2019.119669
Mukadam IZ, Machhi J, Herskovitz J, Hasan M, Oleynikov MD, Blomberg WR et al. Rilpivirine-associated aggregation-induced emission enables cell-based nanoparticle tracking. Biomaterials. 2020 Feb;231. 119669. https://doi.org/10.1016/j.biomaterials.2019.119669
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, Jo Ellyn ; Gorantla, Santhi ; Garrison, Jered ; Gendelman, Howard E. ; Kevadiya, Bhavesh D. / Rilpivirine-associated aggregation-induced emission enables cell-based nanoparticle tracking. In: Biomaterials. 2020 ; Vol. 231.
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