Mcl-1 small-molecule inhibitors encapsulated into nanoparticles exhibit increased killing efficacy towards HCMV-infected monocytes

Christine M. Burrer, Helen Auburn, Xu Wang, Juntao Luo, Fardokht A. Abulwerdi, Zaneta Nikolovska-Coleska, Gary C. Chan

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Human cytomegalovirus (HCMV) spreads and establishes a persistent infection within a host by stimulating the survival of carrier myeloid cells via the upregulation of Mcl-1, an antiapoptotic member of the Bcl-2 family of proteins. However, the lack of potent Mcl-1-specific inhibitors and a targetable delivery system has limited the ability to exploit Mcl-1 as a therapeutic strategy to eliminate HCMV-infected monocytes. In this study, we found a lead compound from a novel class of Mcl-1 small-molecule inhibitors rapidly induced death of HCMV-infected monocytes. Moreover, encapsulation of Mcl-1 antagonists into myeloid cell-targeting nanoparticles was able to selectively increase the delivery of inhibitors into HCMV-activated monocytes, thereby amplifying their potency. Our study demonstrates the potential use of nanotechnology to target Mcl-1 small-molecule inhibitors to HCMV-infected monocytes.

Original languageEnglish (US)
Pages (from-to)40-46
Number of pages7
JournalAntiviral Research
Volume138
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

Keywords

  • Cytomegalovirus
  • Monocytes
  • Myeloid cell leukemia 1
  • Nanoparticles
  • Small-molecule inhibitor

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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